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探索你的基因蓝图 - 由 Sharon Terry 主持的小组讨论

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已经对其基因组进行测序的人们讨论了他们的动机、隐私、数据共享以及解释遗传信息的挑战。

国家人类基因组研究所 · 发布于 2011-02-16 · 1 小时 00 分钟 · 英语 · 许可证：CC BY 3.0 · 来源：在 YouTube 上观看

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AI生成的摘要

本次会议是遗传联盟的Sharon Terry主持的关于个人基因组学的下午专题讨论会，此前由NHGRI的Mark Guyer作介绍。讨论嘉宾是已经对自己的基因组进行过测序的人：NCBI的Stephen Sherry、ClinSeq参与者Rick Del Sontro、杜克大学的Misha Angrist，以及冷泉港实验室的James Watson。他们描述了自己进行测序的动机，包括家族健康史和子女，并讨论了数据共享、隐私、存储以及咨询规模化困难的问题。Watson描述了测序如何改变了他对β受体阻滞剂的使用，将他儿子的神经阻滞剂恶性综合征与药物代谢联系起来，并主张普通人乃至普通医生都不应直接查看基因组，需要顾问并最终需要专科医生。讨论小组还探讨了是否每个人都应该进行测序、基因专利，以及闭幕致辞，指出该领域已取得多大进展，目标是建立希望而非炒作。

根据文字记录生成。请对照原始视频检查链接段落。

带时间戳的章节摘要

关于个人基因组学的下午专题讨论会介绍

[0:00] NHGRI院外研究部主任Mark Guyer接任下午会议的主持。
[0:22] 遗传联盟总裁兼首席执行官Sharon Terry被介绍来主持专题讨论。
[1:09] Sharon Terry有两个孩子患有一种叫做弹性假黄瘤的隐性遗传病，她的本职工作是大学牧师。
[1:30] 她的兄弟死于多形性胶质母细胞瘤，她与早衰症基金会以及提到的其他人是朋友。
[1:43] 她在23andMe一推出时就几乎立刻加入了，最近又参加了ClinSeq。
[1:57] 她说，边走边收集样本虽然被称为非常困难，但一旦合适的系统到位，包括公民科学家的参与，就不会困难了。
[2:27] 讨论小组由已经对自己的基因组进行过测序的个人组成，他们将回答两个问题、互相提问，并接受观众提问。
[3:07] 讨论嘉宾依次为国家医学图书馆的Stephen Sherry博士、ClinSeq参与者Rick Del Sontro、杜克大学的Misha Angrist，以及冷泉港实验室的James Watson博士。

NCBI研究消费者基因组学的研究员

[3:44] Stephen Sherry说他对生物学在基因组学中的前景感到兴奋，并已专业从事这方面工作约10年。
[3:51] 他在NCBI工作了13年，帮助开发变异资源，主要是dbSNP和dbGaP。
[4:13] 他此前没有参加过医学研究，但买了23andMe基因组分型试剂盒作为圣诞礼物送给家人。
[4:36] 他还没有收到结果，所以与讨论小组中的其他人不同，他无法多谈这如何改变了他的想法。
[4:49] 在NCBI，他非常关注与医学研究中参与者的关系，他们的志愿精神和信任至关重要。
[5:15] 他预计基因组学将更多地提供给消费者，但并非每个消费者都会主动寻求信息。
[5:25] 每个家庭中很可能有一个学过生物学或懂一些遗传学的关键人物，成为解读基因检测的首选权威。
[5:39] 他的父母曾带着检测问题来找他，包括他父亲的退行性脑部疾病，所以他现在亲自为家人解读数据。
[5:58] 他认为更多地与23andMe和其他信息提供者接触，将有助于为图书馆的设计决策和信息结构提供参考。

外行人的家族心脏病历程

[6:19] Rick Del Sontro不是科学家，而是一个从不同角度看待这个话题的外行人。
[6:31] 他曾经相信一个神话：体育锻炼、适当饮食、控制胆固醇和低甘油三酯意味着他正走在成功的道路上。
[6:46] 他的母亲在69岁时死于第三次开胸手术期间，他的祖父在成为最早接受开胸手术的100人之一后死于心脏病。
[7:06] 他的姐姐当时大约48岁，感觉不对劲，去看了心脏病专家，发现三处堵塞——两处放了支架，一处没有——并鼓励家人去检查。
[7:32] 他姐姐的总胆固醇水平约为104，至今仍然如此，没有服用他汀类药物，因为她的身体对这类药物反应不佳。
[7:51] 他的普通医生让他做带心电图的跑步机测试，他说这基本上只能告诉你是否会因心脏病发作而倒下；他的检查结果正常。
[8:07] 他的兄弟当时38岁，胆固醇约为150，甘油三酯低且身体活跃，做了核素负荷试验，并在38紧急接受了双搭桥手术。
[8:26] 在惊慌失措并去看心脏病专家后，一次心脏扫描显示他的钙化程度极高，导管检查发现没有严重到需要放支架的堵塞。
[9:12] 在恢复期间，有人告诉他NIH有一项名为ClinSeq的研究，并建议他可能是合适的人选，于是他打电话并同意参与。
[9:39] 他把家族史提供给了研究人员，他们很兴奋，大约一个月后打电话问他全家是否愿意参与。
[10:30] 这项研究层层扩展，追溯祖先至意大利，检测了大家庭和表亲，而他本人已完成全面测序。
[11:24] 他告诉研究人员他想知道测序的发现，就在圣诞节前，他们打电话请他过去，说发现了一些情况。

患者的HNPP诊断与动机

[11:54] 医生将离开一周，所以结果要等到一月中旬。
[11:58] 工作人员说他们不被允许透露他们发现了什么的任何线索。
[12:10] 测序发现了一种称为HNPP的病症，而演讲者此前并不知晓。
[12:19] HNPP会导致身体部分区域出现偶发性麻木，可持续数天、数周甚至数月，并且自演讲者大约20岁时就开始了。
[12:45] 演讲者还了解到自己可能是某些疾病的携带者，其中大多数似乎很罕见，没什么可担心的。
[13:02] 演讲者进行这项研究不一定是为了自己，甚至可能不是为了自己的孩子，而是为了孩子的孩子。
[13:16] 演讲者将蓝图的价值比作GPS，可以建议更好的方法来预防事物或避免某些情况。
[13:50] ClinSeq研究工作人员的精力和热情令人惊叹。

从遗传学实验室到个人基因组

[14:22] 演讲者关注的是遗传学的存在价值，而非临床或个人效用。
[14:28] 演讲者大约从25岁到35岁在人类遗传学实验室度过，作为一名有资格认证的遗传咨询师。
[14:48] 他们研究了一种出生缺陷，发现了一些孟德尔突变，但实验室没有CLIA认证。
[14:57] 由于实验室没有CLIA认证，他们无法将结果反馈给所研究的患者和家庭。
[15:05] 实验室最终获得了CLIA认证，但早期与被研究者之间的脱节让演讲者难以忘怀。
[15:16] 多年后，演讲者在《科学美国人》上读到了George Church的《所有人的基因组》。
[15:31] 这篇文章表达了演讲者的感受：是时候考虑将这项技术推向世界，以及何时开始对健康人进行测序。
[15:54] 这促使演讲者加入了George Church的个人基因组项目，进行测序，公开基因组，并思考其影响。

James Watson谈个人基因组测序

[16:45] 大约五年前，454的创始人提出以合理的成本为Watson测序，并问他是否愿意成为第一个被测序的人。
[17:11] Watson立刻同意了，并说他不如将其公开，但不想知道任何关于载脂蛋白E的信息，因为他的祖母在90年代中期死于阿尔茨海默病。
[17:42] 两年后，创始人打电话说Watson的测序完成了一半，与休斯顿基因组中心和Gibbs团队合作，George Winsock是关键人物。
[18:08] 在贝勒医学院基因组中心的宣传活动中，Watson被告知他是许多坏基因的杂合子，包括BRCA1的一个变体。
[18:31] 他们还告诉他，他是某种可怕的DNA修复疾病的纯合子，他不以为然，因为如果真有这种病，他不可能活到这个年纪。
[18:48] Watson考虑告诉他的侄女们关于乳腺癌基因变体的事，因为犹太变体很糟糕，但他们不是犹太人。
[19:03] 在打电话给侄女们之前，Watson请Mary-Claire King查看他的公开序列，她报告说他有一个无害的爱尔兰变体。
[19:57] Craig Venter的一篇有用文章比较了他的序列与Watson在细胞色素P-450药物代谢酶上的差异；Craig没问题，但Watson有一个代谢非常慢的变体。

个人基因组测序与药物代谢

[20:21] CYP2D6代谢β受体阻滞剂和抗精神病药，使其成为一种重要的酶。
[20:30] β受体阻滞剂让演讲者昏昏欲睡，所以他不得不停止服用。
[20:43] 测序后，他从每天服用β受体阻滞剂改为大约每周一次，现在这控制了他的血压。
[20:57] 一位生物伦理学家提出了一个问题：对自己进行测序是否侵犯了子女的隐私。
[21:19] 他的儿子患有精神分裂症，服用了抗精神病药后出现了神经阻滞剂恶性综合征，差点丧命。
[21:48] 演讲者认为解释是他的儿子没有代谢这些药物。
[22:02] 他的儿子不想对自己的DNA进行测序，但演讲者知道儿子是杂合子。
[22:09] 一些精神科医生现在在给精神分裂症患者服用抗精神病药之前会进行这项检测。
[22:31] 他主张，在不知道患者是否能代谢药物的情况下，不应给任何人服用降压药。
[22:45] 代谢因人而异：有些人是慢代谢者，有些是超快代谢者，对有些人则从不起作用。
[22:50] 对于大型健康保险公司来说，进行这项检测可能具有成本效益。

基因组祖先与阿尔茨海默病测序的局限性

[23:06] Kari Stefansson 在《伦敦时报》上宣布，他查看了演讲者的基因组，发现他有16%的黑人血统和百分之六的亚洲血统。
[23:16] Stefansson 从未发表他如何得出16%的黑人血统和百分之六的亚洲血统的结论，这与家族谱系不符。
[23:32] 演讲者推测，亚洲血统的结果可能意味着田纳西州的某位Watson与一位印度妇女有染。
[23:42] 演讲者没有兴趣追查，也没有将DNA发送给23andMe，宁愿保留自己只是英格兰、苏格兰和爱尔兰血统，没有威尔士血统的传说。
[24:10] 他不想打破自己的传说，因为那可能会揭示德国血统或其他他不想要的东西。
[24:27] 他感到惊讶的是，没有人查看他的序列并撰写发现，这表明人们对他完全缺乏兴趣。
[24:44] 454无法做的一件事是数T，而载脂蛋白E是关键，根据Allen Roses的工作。

TOMM40基因变体与阿尔茨海默病风险

[24:57] 所讨论基因的相邻基因称为tom-D，代表Aldrich线粒体膜，是一个孔道。
[25:06] 人们有长或短两种版本，并且它与aprol基因紧密相关，因此三者有其自身的tom-T多态性。
[25:20] 一个约50的长序列对阿尔茨海默病是非常糟糕的预后指标。
[25:27] 拥有那个长序列并且是三个，患阿尔茨海默病的几率大约是80%；如果是短序列，你就相当安全。
[25:38] 那些从未被测量过的人将不得不回到Sanger测序，或者Pacific BioSciences可以做到。
[25:54] Watson说，查一下Craig的tom-T会很有趣，因为他公布了他的全部序列，但如果他是Craig，他就不会查，因为他60并且正在变老。
[26:20] 一个糟糕的四加上一个长的tom-T意味着你在60多岁时有患阿尔茨海默病的可能。

基因组披露与医学判断

[26:41] Watson认为普通人根本不应该查看基因组，甚至认为普通医生也不能。
[26:47] 需要顾问，以便医生可以询问基因组信息是什么，从而更好地治疗他们的病人。
[26:57] 医生必须运用判断力，不要告诉病人诸如他们会死于亨廷顿病之类的发现。
[27:12] 老式医学和常识应该意味着只告诉人们有用的东西，而不是那些只是另一个担忧理由的事情。
[27:27] Watson看不到任何监管的方法，也不希望它被监管。
[27:37] 他不知道你怎么能获得一张证书，证明你有能力查看基因组并预测某人的未来。

个人基因组学：谁告诉你什么

[28:10] 5AM Solutions的一款名为Snip Tips的新工具允许用户下载他们的23andMe序列，并标记任何文章中提到的每个SNP，点击时显示用户的变异。
[28:20] 越来越多的工具使基因组信息 readily available 供个人检查。
[28:29] 小组被问及谁应该知道什么，以及谁应该告诉人们他们知道或不知道什么。
[28:33] 至少科学界普遍认为，这些都不适合他们所谓的黄金时段。
[28:40] Stephen Sherry博士与他的父母讨论了他们希望了解什么，他们预计几周内会有结果。
[28:49] 他的父母，70多岁，对药效细胞色素结果和药物敏感性非常感兴趣，包括他汀类药物和剂量发现。
[29:09] 他们正在寻找他们的医生或合格的专业人员来解释他们的结果，Sherry说这个职业还没有真正明确。

基因组网络服务中的信任与专业知识

[29:25] Sherry说，网络服务和23andMe的月度订阅模式将让用户随着新发现的发表重新解释他们的基因组。
[29:36] Sherry提出了这些服务有多准确或是否过度简化的问题，他认为这是风险所在。
[29:45] Watson说，对于相当重要的事情，他会非常害怕信任网络。
[29:51] Watson打电话给Mary-Claire King，她了解BRCA1中的所有变异，作为第二意见。
[30:02] Watson认为需要专家，因为你不能相信数据库是完美的，而且决定太重要了。
[30:32] Watson预计最终必须有值得信赖的人类专家，专门研究免疫系统基因或关节炎等领域的医生，而不是一般执业。
[30:55] Watson质疑谁把信息放在网上，以及FDA是否认证了它，并说即使认证了，数据也可能太旧，你不会想使用它。
[31:21] Watson说，整个事情将有利于那些富有并能获得良好建议的人，随着时间的推移，它会向下渗透；他看不到有什么能改变这种情况。

解释基因组数据及其成本

[31:39] 医生可能开具测试，但无法解释，然后交给病人，营利性公司也可能这样做。
[31:49] James Watson博士感到有责任，因为大多数人不像Eric那样知道数据意味着什么；这太复杂了。
[32:01] Stephen Sherry博士的父母在一种脑部疾病的基因测试中经历了这种情况：医生说他不知道如何解释，并把它交给了他的父亲。
[32:13] Watson认为，随着时间的推移，几乎会有一个医学专业，可能涉及不善于社交或自闭症的人负责数据的意义，他们永远不必与病人交谈。
[32:45] Watson说确实有需求，这些信息学人员有工作。
[32:58] Watson说必须有人付钱请人研究基因组；George Church告诉他，检查某人的基因组是要花钱的。
[33:21] Watson很容易看出花费$10,000或$20,000请人查看基因组，而且随着更多区域可以被检查，成本会上下波动。
[33:51] Watson说，在害怕学到东西之前，你应该寻求第二意见。

SNPedia与个人基因型数据

[34:12] Misha Angrist前一天晚上检查了SNPedia，因为他所有的数据都在那里。
[34:18] SNPedia是由两个人在他们的地下室创建的，并链接到GWAS和遗传关联文献。
[34:37] Angrist在SNPedia上大约有9,000或10,000个注释基因型，这基于等位基因频率和疾病严重程度做出主观评估。
[34:59] 他列表的顶部说，他最有趣的SNP是他是个男性。
[35:22] 其他条目包括表型上明显（如果不算恭维）的事情，比如7X的男性型脱发风险。
[35:35] Angrist 将此类结果视为一种教育工具，用以理解例如他为何正在脱发，并或许在较为表面的层面上洞察生化通路。

个人基因组学的动机与问题

[36:28] Rick Del Sontro 表示，在这个问题上他站在 Misha 一边。
[36:36] Rick 说他的检测其实是为了他的孩子和他们的孩子。
[36:41] 他想知道所发现的东西是否可能对他们产生影响，以及是否可以采取什么措施来预防。
[37:03] 他说，听 Watson 博士讲话可以明显看出，还有更多更关键的问题可能被发现，并且会令人担忧。
[37:21] 他将其比作全科医生让他上跑步机做心电图，然后说他没有心脏病。
[37:35] Rick 向 Sherry 博士问了两个问题，首先是她在圣诞节是否收到了这些检测，以及她为周一的 Valentine's Day 准备了什么。
[37:52] 他问是否是她的父母启发了这件事，以及她是否想更多地了解可能导致大脑问题的原因。

NCBI 科学家谈个人基因组共享

[38:07] Stephen Sherry 博士说，大脑问题是一种遗传性生成疾病，他父亲去年夏天为此接受了检测，这让他开始思考这件事。
[38:16] 他指出，一项为期 12 年的 NIH 与 Genome Institute 计划在发现变异目录方面发挥了引领作用，而 NCBI 的任务之一就是维护该目录并将其与疾病关联起来。
[38:39] 他个人想知道这些数据对他意味着什么，尽管他说他认为自己面临的遗传性疾病并不多。
[39:01] 看到人们自愿将自己的基因型放入公共科学存储库，他觉得自己也应该对这一事业抱有同样程度的投入。
[39:09] 他称公开自己的数据是个人决定，因为这对他人的要求不超过他对自己的期望，而且他想从参与者的角度理解这一过程。
[39:37] 他在圣诞节价格合适时买了这项检测，作为一份关于自身知识的礼物送给身体并不特别患病的父母。
[39:51] 他发现这正在开启关于科学、研究资助以及他们正在学习什么的家庭对话，他认为这对许多美国人来说是一个更广泛的机会。

Watson 谈重测序与遗传担忧

[40:36] 一位小组成员问，除 Watson 博士之外的小组成员是否愿意接受重测序，以讨论过去与新技术以及衰老的影响。
[40:46] Watson 开玩笑说，他这个年龄的人中大概有 80% 听不见。
[41:01] Watson 说，不，他不想接受重测序。
[41:21] Watson 回忆说，有人告诉他，他与那个坏碱基只差一个碱基对，所以他从未处于风险之中。
[41:32] Watson 说，他尽量不做爱担忧的人，并避免会让他担忧的信息。
[41:53] Watson 强调，细胞色素在医学治疗中相当重要，他说除了让小公司来做之外，他想不出任何办法能足够快地惠及普通人。
[42:17] Watson 说，β受体阻滞剂确实能控制血压，而 80 岁以上的人中有 80% 的血压高到必须加以控制的程度。
[42:43] 一位发言者问，所发现的动脉钙化基因是否与 Gall 博士团队测序的外周动脉钙化基因相似。
[43:01] Rick Del Sontro 回答说，他就是不知道。

Watson 谈祖先与数据存储

[43:15] Bert Gold 自我介绍说他在 National Cancer Institute 工作。
[43:25] Gold 告诉 Watson，他也能像 Jerry Seinfeld 一样做单口喜剧。
[43:54] Gold 说，查看 Watson 在 Duffy 位点的 DNA 表明，Watson 至少是 Duffy 杂合子，这暗示其可能比其他来源更晚近地源自非洲。
[44:21] Gold 问 Watson 认为这是 DNA 错误，还是更认同苏格兰或爱尔兰血统。
[44:33] Watson 回答说，他对此没有想法。
[44:40] Watson 说，Kari Stefansson 有理由不喜欢他，而他也有理由不喜欢 Stefansson，他曾在一次会议上称他为水蛭。
[44:58] Watson 形容 Stefansson 是冰岛人，身高约六英尺八英寸，像 Craig Venter 一样个性很强，并说像 Craig 一样，他也做过一些好事。
[45:44] Watson 说，祖先这件事有点无关紧要，他讲笑话是因为他坦白说根本不在乎。
[45:47] 一位男性发言者问小组，鉴于有多个供应商、公司和技术对 DNA 进行测序，并且一个人自己的 DNA 会有多个副本，这类数据今后将存储在哪里。

个人基因组数据的存储与隐私

[46:00] 该发言者问，消费者是会自己追踪他们的序列数据，还是依赖可信的中央存储库，并指出有许多未决问题。
[46:15] Stephen Sherry 博士认为，人们会像对待音乐下载一样对待它，个人库或私营公司会进入市场。
[46:26] Sherry 说，除了为了提高效率或方便个人之外，并不需要集中化。
[46:33] Sherry 说，政府数据库并不合适，因为这不是研究，也没有为此提供资金。
[46:42] Sherry 指出，他和其他人的数据将进入公司数据库，这些数据库可能会被出售给新公司，而这一切都包含在知情同意中。
[46:50] Sherry 计划通过下载并整合来保留一份个人副本。
[46:56] Misha Angrist 认为，对大多数人来说，它可能会存在于云端，而一些担心隐私的人会坚持让它放在自己的床头柜上，或者不放在公共或远程位置。

扩大遗传数据共享与咨询

[47:27] 一位遗传咨询专业的学生询问，对基因检测的控制权是早期采用者的特权，还是每个人都应拥有的权利，以及如何扩大其规模。
[48:15] Rick Del Sontro 表示他当时不知道发生了什么，没有看到数据，只拿到结果，并且乐意与任何人分享这些结果。
[48:53] Rick Del Sontro 无需支付测序费用，因为这是作为研究的一部分支付的，并且他理解全测序相当昂贵。
[49:10] Misha Angrist 表示早期采用者享有特权并得到了大量手把手指导，随着更多人参与，这变得难以规模化。
[49:27] Misha Angrist 表示，为所有人扩大实体遗传咨询的规模，部分催生了23andMe 这样的公司以及向软件的转变。
[49:58] Stephen Sherry 博士希望有一种清晰的方式，在其他人接受检测时与直系和扩展家庭成员分享结果，然后在查看后向全世界公开。
[50:21] Stephen Sherry 博士不准备像个人基因组那样把结果公之于众，因为不知道会发生什么，并认为应该在同意过程中 upfront 做出承诺。
[50:30] Stephen Sherry 博士认为消费者模式将更加渐进，并且明确提供和构建这一点对于伦理至关重要，因为它会触及后期采用者。

保险、遗传数据与隐私

[51:04] James Watson 表示他会与保险公司分享他的数据。
[51:17] Watson 建议大型项目只对70岁左右的人进行测序，因为他们的完整既往病史可获取，而且退休人员可能不担心公开信息。
[51:47] Watson 认为需要与基因型相关的表型来解释遗传数据，而过多的保密使解释变得困难。
[51:53] Watson 表示他并不担心，部分原因是他的年龄，因为他不会被发现携带亨廷顿病基因。
[52:16] Watson 表示人们更有可能受益，就像他帮助儿子那样，并且可能了解到自己是囊性纤维化的携带者，从而他们的孩子应该检查。
[52:42] Watson 表示他大体上不会担心测序，并认为这种担忧被夸大了。
[52:49] Misha Angrist 指出，除了 Jim 的 APOE 位点外，他们两人的基因组都是公开的，所以保险公司不必问他们。
[52:59] Watson 表示保险公司缺乏解释基因组所需的数据，并建议人们不要了解或公开它，因为没有好处。
[53:40] Watson 表示目前法律禁止保险公司使用这些信息，并引用了 Francis 推动通过的反歧视法。
[53:53] Watson 称保险歧视是我们最不用担心的问题。
[53:59] Stephen Sherry 区分了分享遗传信息和表型信息，指出他母亲对23andMe 调查收集表型（如胸罩尺寸）的担忧。
[54:17] Angrist 表示这可能是双刃剑：知道自己 ApoE4 纯合且未分享的人可能会大量购买长期护理保险。

每个人都应该进行基因组测序吗？

[54:51] Ahmed Kablan 询问，对每个人的基因组进行测序并告知他们 SNP 或可能的遗传疾病风险是否是正确决定。
[55:06] Kablan 指出，告诉某人他们可能在20年后患上阿尔茨海默病或痴呆症只是一种预测，而非确定性，并且除了遗传外还取决于环境和其他因素。
[55:26] Kablan 表示有些人可能无法很好地接受这样的消息，可能会崩溃。
[55:44] Rick Del Sontro 回答不，这不适合所有人，并且需要对告知人们的内容进行一些过滤。
[55:58] Del Sontro 表示有些人是担忧者，他们能处理好这些信息，而另一些人则处理不好。
[56:21] Del Sontro 表示知道真正灾难性的事情会改变你每天看待和应对生活的方式，可能不健康，但你能控制的事情知道则很重要。
[56:46] Del Sontro 表示如果他将会患上亨廷顿病，他不确定自己是否一定想知道。
[56:49] James Watson 博士表示他会起诉告诉他这一点的医生，因为不必要地扰乱了他未来的生活。
[56:56] Watson 表示你必须有一些常识。
[57:05] Watson 表示如果有人想知道，当然可以，尽管他们承担着很大的风险。

基因专利辩论

[57:25] 一个法律问题指出，学术界和媒体对基因组序列专利化有大量讨论。
[57:34] 发言者询问，一个特定的使幽默成为可能的基因组是否可以申请专利并保留给一个人。
[57:49] James Watson 博士表示他因反对基因专利而被解雇，并且此类专利阻碍了遗传学的发展。
[58:13] Misha Angrist 指出，去年纽约的 Sweet 法官对 Myriad Genetics 的一些 BRCA 基因专利作出了不利裁决，该裁决正在上诉中。
[58:34] Angrist 认为这些专利中的大多数将在本十年内到期。
[58:34] Angrist 预计单基因疾病的基因专利可能会自然消亡，尽管他说这可能是如意算盘。

基因组学小组闭幕词

[58:52] 人们通过多种方法和预言了解了自己的序列。
[58:59] 十年前这个小组讨论不可能实现，显示了该领域已经走了多远。
[59:07] 发言者表示，我们尚未开始探索一百万个基因组在社会背景下意味着什么。
[59:17] 10年前，在世界各地互相卖书似乎很疯狂，但今天却很容易。
[59:25] 随着需求的出现以及个人与NIH、Wellcome Trust和其他实体的合作，这些问题可以共同解决。
[59:36] 目标是建立希望，而不是炒作。
[59:40] 发言人请观众一起感谢小组成员。

[0:00] Mark Guyer：欢迎回到下午的会议。我是Mark Guyer。我是NHGRI院外研究部的主任，我将接替主持今天下午的会议，好让Eric放松一下，这是我听过的最矛盾的说法。我将继续Eric开始的方式，邀请我们的小组成员上台。并介绍Sharon Terry，Genetic Alliance的总裁兼首席执行官，她将主持小组讨论。

[0:34] Sharon Terry：非常感谢，Mark，也感谢规划委员会，到目前为止真是美好的一天。我想下午也会同样美好。规划委员会的卓越之处——大家可以就座了——在于他们足够明智，知道人们及其与自身基因组的各种关联形式也需要成为本次研讨会的一部分。我之所以这么说，是因为我有两个孩子患有一种叫做弹性假黄瘤的隐性遗传病。我本职是一名大学牧师，但现在非常融入这个领域，也很高兴能成为其中一员。我的——我也非常关注我们今天上午看到的所有信息，并像许多公众一样，等待着我们希望看到的各类解决方案、疗法、检测等等。我的兄弟死于多形性胶质母细胞瘤，所以我

[1:34] 很高兴看到这作为早期项目进入各种计划。然后我和Progeria Foundation以及我们到目前为止提到的其他几个机构都是很好的朋友。我也是那种23andMe一推出就几乎立刻使用的人，最近还加入了ClinSeq[按发音拼写]，我们今天会稍微听到一些相关介绍。所以我对我们自己的基因组以及我们能利用这些信息做什么非常感兴趣。我想说的是，我认为随着进展收集样本——今天上午肯定多次提到过，而且说非常困难——将会像我们以为会非常困难的其他许多事情一样。那就是，一旦我们允许正确的系统到位，包括公民科学家的参与，那些明白自己需要参与的人，我指的确实是我们所有人，我们每一个人，尤其是通过社交网络，将开始理解以各种方式为科学所用的重要性。

[2:27] 今天，我们将听到几位已经完成基因组测序的人发言，他们对在个人层面上理解这一点有着极大的兴趣。我们将请他们在简短的自我介绍中回答两个问题。然后我们会请他们互相提问，之后我们会邀请你们向他们提问。所以这个小组讨论持续大约一个小时，会比一些其他环节更具互动性。所以你们应该准备好向这些人提出任何你们想问的问题。

[2:57] 我也将省去正式介绍，只告诉你们他们的姓名和所属机构。我还会告诉你们他们出场的顺序，尽管他们已经在这里了。首先，我们将听取国家医学图书馆的Stephen Sherry博士发言。然后我们将听取ClinSeq参与者Rick Del Sontro发言。接着我们将听取杜克大学的Misha Angrist发言，最后是冷泉港实验室的James Watson博士。再次说明，每人将用大约五分钟介绍自己，然后我们将进入他们之间的对话，之后是你们的提问。

[3:37] 那么，Steve[按发音拼写]，你可以开始了。Stephen Sherry博士：谢谢你，Sharon。我想说，我对生物学在基因组学中的前景感到兴奋。我从事这项工作 professionally 大约10年，在NCBI工作了13年，我在那里负责或帮助开发变异资源，其中主要是dbSNP和dbGaP。因此，在我的整个职业生涯中，我与基因组信息有着科学上的关系，并好奇地观察着消费者试剂是如何开发的，以及这对个人意味着什么。我以前没有参加过医学研究，但今年23andMe在圣诞节期间出售基因组分型试剂盒，所以我为家人买了它们。我想这会是给我父母的一份很棒的圣诞礼物，他们什么都有，你知道，你能给他们什么呢？

[4:31] [笑声] 现在这将变成一连串强迫症般的问题，比如他们对他汀类药物的药物敏感性以及各种各样的事情。我还没有收到我的结果，所以与这个杰出小组中的其他人不同，我没有太多可说的关于这如何改变了我的想法。我或许可以简短地谈谈我为什么决定这样做[听不清]纯粹的好奇心。在NCBI开发这些目录、这些资源时，我们非常关注我们与医学研究参与者之间的关系。他们的志愿精神、他们的信任对科学研究中的关系至关重要。因此，我们正在努力确保我们在医学图书馆开发的资源既能满足他们的需求，也能满足研究界的需求。

[5:15] 我们设想的是，今后基因组学将更多地惠及消费者——但并不是每一位消费者都会主动前来寻求信息。最有可能的情况是，每个家庭中都会有一位关键人物，他/她大学时学过生物学，或者懂一些遗传学，并会成为家庭关系中的权威、那个被大家找去说“帮我解读一下我的基因检测结果”的人。就我个人的经历而言，我的父母曾来找我，说，你知道，我父亲有一种退行性脑部疾病，这意味着什么，你知道，他们的检测结果。所以我现在看待他们，不再是以一个理论研究者、只求确保信息完整的视角，而是试图为我自己的家人亲自解读这些数据。因此我在想，我越是能参与到 23andMe 以及其他这些正在消化信息的信息提供者中去，就越能帮助我们在设计决策上获得参考，也有助于我们在图书馆提供的信息结构中的资源建设，因为我们努力服务的是所有人，包括纳税人，以及我们的研究社群。这有点[听不清]——我就说到这里。

[6:16] Sharon Terry：太好了，非常感谢。Rick？Rick Del Sontro：嗯，我是从一个完全不同的角度来看这件事的。我不是科学家，我只是个普通人。我的故事还挺有意思的。我曾经深信那个神话：只要我身体活动多、吃得对、把胆固醇控制住、甘油三酯低，你知道，我就在通往成功的路上。我的母亲在69岁时、在她第三次开胸手术期间去世，我的外祖父也死于心脏病，他还是最早接受开胸手术的100人之一，所以我一直对此很敏感。几年前，我妹妹当时，我相信是48岁，她开始感觉不对劲。于是她去看医生，医生把她转诊去看心脏病专家。长话短说，她——结果发现她

[7:20] 她有三处堵塞，其中两处放了支架，一处没有放，她强烈鼓励家人去做检查。现在，我来自一个大家庭，有八个孩子。有意思的是，我妹妹的胆固醇水平，总胆固醇水平，大约是104，而且至今仍然如此，没有服用他汀类药物，因为她——她的身体对这类药反应不好。所以，总之，我就去看了我的医生，你知道，又是那位我看了多年的普通全科医生，他让我上了跑步机，接上心电图机，那基本上只能告诉我，我猜，我是不是快要因为心脏病发作而倒下。所以我检查结果没问题，就回家了。当时我有一个哥哥，他38岁，胆固醇水平大约150，甘油三酯低，身体活动多，他去做了核素负荷试验。他们不喜欢看到的结果，就做了导管检查。他进去

[8:21] 在38岁时接受了紧急双搭桥手术。于是我慌了，去看了一位心脏病专家。他走进房间，看了看我的档案，说：“你来这儿干什么？”我说：“你看，先让我给你讲讲我的故事，如果之后你真的还想让我走，我就走。”于是我就跟他讲了，他觉得挺有意思。他让我去做一次心脏扫描，我做了。结果回来显示我的钙化程度高得离谱。所以那时候，我接受了一系列检查。他说，我们真正搞清楚状况的唯一办法就是做导管检查，那是你唯一能获得安心的办法。所以我做了，幸运的是，我的堵塞没有一处严重到需要放支架。当我躺在恢复室里——我想你得平躺四五个小时——有人走过来对我说：“NIH 那边正在做一项研究，叫，你知道，ClinSeq。你可能会对这个感兴趣

[9:23] 而且你可能是合适的人选，一个很好的候选人，可以去那边。”于是我打了又打，终于有人给我回了电话。我说：“好，我愿意参加。”[笑声] 嗯，他们正忙着做研究，你知道，外面有很多 DNA，你知道。所以总之，我去了，告诉他们我的家族史，说实话，在我讲述的过程中，告诉他们，你知道，过去发生了什么、现在正在发生什么，他们对整件事真的特别兴奋。所以，他们那天做了一堆检查，大约一个月后，我接到一个电话，我能——我真的没太听懂，但我能感觉到他们对某件事很兴奋。他们说，你知道，“我们认为我们在这里发现了相当、相当有意思的东西。”我说：“好，太好了。”他们说：“你觉得你全家人都愿意参与这项研究吗？”我说：“当然，但他们不都住在本地。”他们说：“哦，别担心，你知道，就看看他们愿不愿意来参与。”所以，你知道，我联系了他们所有人，说：“你们愿意来试试，去参与

[10:25] 做研究。他们正在做一项关于心脏疾病和你的DNA的研究。”好，行，他们会去的。所以我觉得从那时起，这件事可以说就开花结果了，这是我能想到的最好的说法。这项研究现在已经层层深入，事实上我进来之前刚和Biesecker医生[按发音拼写]聊过，他们已经做了一些家族病史调查，把祖先追溯到了意大利。我想他打算去那边走一趟，而且他们现在已经检测了扩展家庭成员、表亲之类的亲属。而我个人已经接受了全基因组测序，所以我经历了那个过程，当时完全不知道那是什么。他们说：“哇，你知道那是什么吗？”我说：“不知道，我对那意味着什么毫无头绪。”[笑声][听不清]还有Watson医生，我不是有意，你知道，我只是——[笑声]——抱歉。我是个外行，我就是个普通人。所以不管怎样，他们说：“在我们进行测序的过程中，我们会发现一些东西，你想知道

[11:32] 这些吗？”我心里想：“嗯，是的，我想我知道。”于是他们说：“太好了。”所以圣诞节前有一天我接到一个电话，他们说：“你能来一趟吗？”还有，“我们发现了一些东西，想和你谈谈。”我说：“好，那你们想让我什么时候来？”哦，不行，我要去度假了，哦，那之后医生还要离开一周，所以得等到一月中旬了。我说：“哦，那你们能不能给我点提示，你们发现了什么？”“不行，我们不允许那样做。”[笑声]哦，这会是个不错的圣诞节，对吧？总之，结果他们发现了一种叫HNPP的病症，在测序过程中——如果你不知道HNPP是什么，没关系，因为我也不知道。但基本上我会出现麻木；我身体各处会间歇性出现麻木阶段。这从我大约20岁时就开始了。我完全不知道是什么引起的，坦白说也没有别人能告诉我是什么引起的。而我身体的一些部位会

[12:34] 麻木好几天、好几周甚至好几个月。然后最终它会消失。所以我得以更多地了解这方面，随后也了解到一些我可能携带的基因。其中大多数似乎都很罕见，所以没什么真正需要担心的。但以前有人问过我，这如何改变了我？这如何影响了我，意味着什么？这真的很有意思，因为我做这项研究不一定是为了我自己，也许甚至不是为了我的孩子，而是为了我孩子的孩子，因为我认为会有那么一个时刻，你知道，你出生时你的蓝图就摆在面前，你知道该怎么做。我把它比作使用GPS，对吧，你沿着路走，你会遇到堵车，你的GPS会告诉你往另一个方向转弯。你无能为力，你要从A点到B点，但沿途也许——也许有更好的路可走，对吧？也许有更好的事情我们可以做，来预防某些事情或避免某些

[13:36] 情况。所以从我的立场来看，我想知道。我知道外面有很多和我交谈过的人可能会说：“看，我不想知道发生了什么。”但对我来说，知道一直很重要，这让我大开眼界。我要说的是，ClinSeq研究所有工作人员的活力和兴奋之情令人惊叹。真的——他们对自己所做的工作非常兴奋，从我的角度来看，这相当了不起。所以希望这是个不错的背景介绍，可能超过了五分钟，但这就是我的故事。谢谢。

[14:10] [掌声] Sharon Terry：谢谢。Misha Angrist：嗯，这可是个很难接的场。所以我参与这件事——我不打算谈临床效用，甚至个人效用，但也许是存在性效用。我从25岁到35岁左右在一个人类遗传学实验室度过。我是那个有资格参加考试的遗传咨询师。然后我研究了一种出生缺陷，我们实际上发现了一些孟德尔式突变。我们不是CLIA认证实验室；我们无法把结果反馈给那些患者和家庭。最终我们成了CLIA认证实验室，但那种与我们正在研究的人之间的脱节总是

[15:12] 让我耿耿于怀[按发音拼写]。所以很多年后，我翻开《科学美国人》，因为里面有一篇叫《所有人的基因组》的文章，作者是哈佛一位叫George Church的人。我读了那篇文章，感觉这个人说出了我感受到的许多东西，那就是时候开始思考我们如何把这项技术推向世界了，在什么节点我们开始对像我右边这位先生这样的健康人进行测序？于是这就开启了我的这段旅程：我加入了George Church的个人基因组项目，对我的基因组进行了测序，与它共处，把它公开，并思考它的影响。还花了大量

[16:17] 时间面对Excel电子表格，学到了很多关于下一代测序技术的知识。所以，我来了。[掌声] James Watson医生：那大概是将近五年前，454的创始人，一家新的DNA测序公司[听不清]来到我的办公室，他打电话给我，说他想——他们有一台仪器，能够以合理的成本对我进行测序，问我愿不愿意成为第一个被测序的人？所以我立刻说愿意。我不——我说，不妨把它公开，但我不想

[17:19] 对载脂蛋白E有所了解，因为我有一位祖母在90十年代末——不，90十年代中期——死于阿尔茨海默病。那非常可怕，所以我根本不想了解它。后来真的没再想过，两年过去了，他打电话给我说：“你已经完成了一半测序，我们正在与休斯顿基因组中心、Gibbs和他的团队合作——George Winsock［按发音拼写］是关键人物。”然后随着时间推移，你知道，我去了休斯顿，那里有贝勒医学院基因组中心的宣传，他们告诉我，我是许多不良基因的杂合子。他们说我有一种乳腺癌变体，BRCA1。好吧，但是，你

[18:26]知道，我不知道那意味着什么，我认为他们也不知道。但他们告诉我，我在某种可怕疾病的DNA修复[按发音拼写]相关基因上是纯合子，比如Helman病[按发音拼写]。我的意思是，如果你有那种病，根本活不到我这个年纪，所以我根本没去想它。而且——但我确实想过，如果，你知道，我不知道自己在乳腺癌基因中携带的是哪种变体，所以我觉得应该告诉我的侄女们，因为如果你有犹太变体，那是一个很糟糕的基因。我们不是犹太人，所以，你知道，我觉得我不应该有那个变体。

[19:02][笑声]但我想弄清楚——不过在给她们打电话之前，我先打给了Mary-Claire King[按发音拼写]，我的序列在网上。于是她查了一下，给我回电话说，你有一个无害的爱尔兰变体。她怎么知道那是无害的爱尔兰变体，但，你知道。所以我就没再想这件事，也没给侄女们打电话，所以没怎么在意。后来有人打电话给我说：“你还没有删除，或者还没有让我知道你没有从你的序列中删除足够多的内容[听不清]载脂蛋白是，你想知道吗？”当然，我不想知道，我也不能告诉他们不要发表，你知道——但事情更复杂。

[19:57]后来发生了一件真正有用的事，Craig Venter[按发音拼写]的一篇文章发表了，将他的序列与我的序列在细胞色素P-450，即代谢药物的酶方面进行了比较。Craig没问题，但我有一种代谢非常缓慢的2P6[按发音拼写]某种形式，这种形式不仅代谢β受体阻滞剂，还代谢抗精神病药。所以这是一个重要的酶。我曾被开了β受体阻滞剂，它们让我昏睡，我不得不停用。然后突然间我有了答案：与其每天吃一片，也许我应该每周吃一片，我现在就是这么做的，它控制了我的血压。所以那是一个极其有用的事实，如果没有——就不会知道。同时也出现了一个问题，有人说：“那么，在获取

[21:02]自己的序列时，你会了解到一些关于你孩子的事情。你有权侵犯他们的隐私吗？”好吧，不，不，我的意思是，这就是这些，你知道，这些生物伦理学家没别的事可做，只能想这种事。[笑声]而且——结果发现我的儿子，我有一个患精神分裂症的儿子，他在打了一位医生之后被给予了抗精神病药，那位医生是个弗洛伊德派，而我也会打任何弗洛伊德派。

[21:35][笑声]但不管怎样，他打了那位医生，一个非常可怜、肥胖、矮小的男人，还有Chestnut Lodge[按发音拼写]，它现在已经不存在了，但那是[听不清]郊外的一个地方，他得了神经阻滞剂恶性综合征，差点死掉。我想我们现在有了答案，他不能代谢那些药物。所以这是一个非常有用的事实。他不想让自己的DNA被测序，但我知道他是纯合子，所以他是杂合子。而且结果可能是——一些精神科医生现在在给精神分裂症患者开抗精神病药之前真的在检测这个，所以这相当重要。如果我更年轻，而且，你知道，靠学术薪水生活，我肯定会创办一家专门做细胞色素检测的公司，因为任何，你知道，去医生办公室看血压的人都不应该在不知道

[22:37]自己能否代谢药物的情况下就被给予该药物。我的意思是，有些人是——我是慢代谢者，有些人是超快代谢者，药物对他们从来不起作用。所以对大型健康保险公司来说，做这个检测可能具有成本效益。所以我认为，你知道，然后唯一另一件事是，在我从未打算发表的一句评论之后，Kari Stefansson[按发音拼写]在《伦敦时报》上宣布，我——他看了我的基因组，我是16%黑人，百分之四——百分之六亚洲人，这与我家族的谱系不符。而他从未发表他是如何得出我是16%黑人和百分之六亚洲人的结论的，可能，你知道，亚洲人那部分可能意味着田纳西州的某位Watson[按发音拼写]与

[23:38]一位印第安妇女有染。[笑声]而且——但我对此毫无兴趣。所以，你知道，我本可以跟进这件事。我没有把我的DNA寄给23andMe，那可以给我相当不错的祖先分析。但我担心，我，你知道，活在一个神话里：我只有英格兰、苏格兰和爱尔兰血统，没有威尔士血统，而且——[笑声]——所以我不想让它被打破[按发音拼写]。你知道，那是个神话，为什么要毁掉我的神话？它可能会发现我有德国血统之类的，你知道，那是我本不想要的。所以，你知道，这就是我的立场，我异常地不好奇。而且——但让我惊讶的是，你知道，人们真的没有看过我的序列并写文章说他们发现了什么。所以据我所知，人们似乎对我完全缺乏兴趣。

[24:39] [笑声] 你知道，人们对我评价好或坏。然后话题转到阿尔茨海默病上；谁有趣，我[按发音拼写]。454做不到的一件事就是数T[按发音拼写]，你知道。结果发现，载脂蛋白E，关键所在，Allen Roses[按发音拼写]的工作是，与它相邻的是一个叫tom-D[按发音拼写]的基因，代表Aldrich[按发音拼写]线粒体膜，它是一个孔道[按发音拼写]。人们要么有一个长的——或者视情况而定，它与aprol[按发音拼写]紧密连锁，所以那个三有自己的多态性——tom-T[按发音拼写]多态性。还有一段大约50的长序列，这对阿尔茨海默病是非常糟糕的预后指标。如果你有那段长序列而且你是三，你将会——不，大概80%的几率你会得阿尔茨海默病。如果你有短的那一个，你就相当安全。所以，那些本来永远不会被测量的人，你将不得不回到

[25:48] Sanger[按发音拼写]测序来做，或者Pacific BioSciences可以做。Craig，已经公布了他的全部序列，你知道，查一下他的tom-T会很有趣，如果我是Craig，我不会去看它，因为他60，你知道，年纪大了。

[26:19] [笑声] 而且，你知道，人们确实会，你知道，一个糟糕的四[按发音拼写]加上一个长的tom-T意味着你在60多岁时有得阿尔茨海默病的几率。Sharon Terry：谢谢，Jim，所以你[听不清]——[笑声] Dr. James Watson：总之，这就是[听不清]那个故事，所以——但我想回到那个总体观点。我认为DNA序列应该被知晓。我不认为普通人真的应该去看它们。我甚至不认为普通医生能看它们，必须得有顾问。

[26:52] 医生说，基因组给我的信息是什么，让我能更好地治疗我的病人。然后医生必须表现出分寸，不告诉你我们发现你会死于亨廷顿病，你明白。因为，你知道，那不是好消息。所以必须有老式的医学和常识，你只告诉人们有用的东西，不告诉那些只是又一个担忧理由的东西。我看不出有任何办法来监管它，这只能取决于——我不希望它被监管。

[27:37] 这已经够复杂了，我不知道你怎么能拿到一张证书证明你有能力看一个基因组并预测某人的未来。Sharon Terry：太好了，谢谢Jim。Dr. James Watson：好吧，那就——[掌声] Sharon Terry：所以我想你引出了一个非常好的问题，一个非常有趣的问题，自从基因组对我们这些普通公众、甚至对我们这些在不同领域工作的科学家开放以来就一直在争论。那就是——谁应该知道什么、何时知道，以及谁应该告诉谁什么？我甚至想到——5AM Solutions[按发音拼写]出了一个新工具叫Snip Tips[按发音拼写]。基本上你下载23andMe序列，它会标记你在任何文章中读到的每一个snip，你可以点击它，它就会显示你的变异。

[28:20] 所以越来越多的工具让我们每个人都很容易查看这些东西。我想知道在座是否有人愿意评论一下，你们认为自己应该知道什么，你们认为应该由谁来告诉你们所知道或不知道的事情？而且这也是那种普遍看法，至少在科学界中，认为这些都没有准备好进入他们所说的黄金时段。Dr. Stephen Sherry：我昨晚刚和我父母谈过这件事，想着今天的讨论，问他们几周后拿到结果时希望知道什么。他们对细胞色素结果的药效动力学组合及其对药物的敏感性非常感兴趣。他们70多岁，开始关注他汀类药物和其他问题，想知道当有关药物敏感性或剂量的发现出来时，是否与他们相关。我认为这是一个很好的、你知道的、个人用途。所以我认为，他们在寻找要么由他们的医生来解读结果，要么由专业人员，你知道的，他们[按发音拼写]会被转介给的、合格的专业人员。我不认为那个职业真正被厘清

[29:22] 还没有。Dr. James Watson：现在还不存在[按发音拼写]。Dr. Stephen Sherry：所以网络会为他们做这件事，会是这些网络服务，23andMe本身，它是一个月度订阅模式，随着新发现发表，你可以去重新解读[按发音拼写]你的基因组，或者像你提到的那样。所以我认为有一个问题，就是它们有多——它们有多准确，或者它们是否过度简化？这就是我担心的风险。Dr. James Watson：我会非常害怕信任网络，你知道，对于相当重要的事情。我打电话给Mary-Claire King，我很幸运，因为她知道BRCA1中的所有变异，或者你知道，[听不清]会让她知道。那个——我认为我们将不得不有一些专家，你就是不能相信，你知道，这个数据库是完美的。我的意思是，这些决定太重要了，而且我会，你知道，在寻求第二意见的意义上，我很幸运，认识那个，你

[30:26]知道，那个人可能比世界上任何人都更了解BRCA1，以及你如何获得这个建议。但我确实认为，最终必须要有你信任的人类，他们了解所有的多态性，他们是医生，而且他们不想执业。但他们有点专门研究，你知道，你免疫系统的所有基因，或者，你知道，他们真的了解关节炎。你从他们那里获得帮助。所以我认为必须要有你可以打电话咨询的专家。仅仅因为它在网上，而且，你知道，是谁把它放在那里的，怎么放的，你知道，FDA有没有认证过，如果认证过，你知道，我不会，你知道，数据太旧了，你不会想用它的。

[31:21]所以，你知道，再说一次，你知道，整件事会偏向那些有钱、能获得好建议的人，随着时间推移，它会逐渐向下渗透。我看不出有什么能改变这种情况。Stephen Sherry博士：我能问一下吗，您是否认为一位医生开具检测、收到结果、却不知道如何解读，然后把它交给患者，与一家只为盈利而做检测、直接把结果交给患者的公司之间，有区别吗？James Watson博士：我想我觉得[按发音拼写]有责任，因为，你知道，如果你把它交给Eric，他能，你知道，解读它，但大多数人不会知道它意味着什么。这太复杂了。

[32:01]Stephen Sherry博士：这就是我父母在这种脑部疾病的诊断检测中的经历。检测被开具，基因检测结果回来了，医生说，“我不知道如何解读这个，”然后把它交给了我父亲。James Watson博士：是的，所以我认为，你知道，随着时间推移，几乎会有——不管他们叫它医学专科还是什么。很多不喜欢与人打交道的人，你知道，是自闭症患者，他们可以负责数据的意义，而且他们永远不必与那个生病的可怜人交谈。不，我的意思是，我真的在人类历史上第一次看到这种情况，这些不善社交的信息学人员有——[笑声]——我们有真正的需求，而他们有工作。

[32:52]Stephen Sherry博士：如果我们开放数据——James Watson博士：什么？是的。Misha Angrist：所以您是说这是一个公共工程计划。James Watson博士：不，不，不，不，不，我认为你们最终必须——必须有人付钱让某人研究基因组。我问George Church，我说，“我的基因组意味着什么？”他说，“嗯，你得给我钱，检查某人的基因组是要花钱的。”所以——你知道，而且不是一笔小数目，可能为了得到你的基因组，我很容易看出会花掉$10,000或$20,000[按发音拼写]来让人看看它。从某种意义上说，成本会上升，两者都会上升和下降，因为我们将能够查看更多的区域，因为我们有一些经验表明那些多态性意味着某些东西。我们可以把这一切放在NIH网站上，但我认为对于某些事情，你知道，在我们害怕学习之前

[33:59]某些东西之前，你应该寻求第二意见。这就是我想说的全部。Sharon Terry：让我们听听你对此的想法。Misha Angrist：嗯，所以为了这个所谓的准备，我昨晚上了SNPedia[按发音拼写]，因为我所有的数据都在那里。这是一个基本上由两个人在他们地下室里创办的网站，它链接到文献，所有GWAS和遗传关联文献，所以我有，我不知道，9,000或10,000个注释基因型在那里。它做出一些主观评估，这些似乎是最有趣的片段，它基于等位基因[按发音拼写]频率和病症严重程度等等。所以我看了列表顶部，我说，“我想知道我最有意思的片段是什么，”它说，“你是男性。”

[35:05][笑声]Sharon Terry：经过今天上午之后，我们现在知道这很重要。Misha Angrist：我以为他们把这个搞定了。[笑声]然后，你知道，后面还有一些表型上[按发音拼写]明显、如果不是讨人喜欢的事情，比如，你知道，7X[按发音拼写]男性型秃发的风险之类的。所以我们可以说那是无聊的，我们不需要知道那个，那有什么意义。但我想我把那看作一种教育工具，是的，我知道我在秃顶，但这里有一个机会也许可以理解为什么，并看看今天在这里被如此雄辩地讨论过的任何这些生化通路，只是获得一些洞察，也许在某种表面层面上了解这如何

[36:12]影响我。Sharon Terry：太好了。James Watson博士：祝你好运。[笑声]Misha Angrist：我有时间。Rick Del Sontro：是的，我有点——我想在这个问题上我有点站在Misha这边。再说一次，我的意思是，那里有——当我做检测时，真的关乎我的孩子和他们的孩子。所以如果有什么我发现的，有什么他们能发现的可能影响他们或将会影响他们的东西，有没有什么，你知道，可以做来预防它或阻止他们走上，你知道，一条滑坡。所以——但这很有趣。至少尝试理解事情以及为什么它们发生在我身上，甚至只是，你知道，仅仅这一个病症，这很有趣。但我想在听Watson博士讲话时，很明显有更关键的问题你可以发现，我认为那会

[37:17] 值得关注。而且我会，你知道，这有点像我的全科医生只是让我上跑步机做心电图，说：“看，你没有心脏病。”你知道，我不怪那个人，但同样地，我可能几年前就能发现，你知道，也许我可以做些什么来预防它。所以我的另一件事，如果我能问一个问题，我想问 Sherry 博士——两件事。第一，你说你圣诞节收到了测试？你知道，周一是情人节，你为此准备了什么？

[37:51] [笑声] 不，我是说——那是什么，是你的父母启发了这件事吗？你想更多地了解可能导致这种情况的原因吗，你知道，大脑问题？那到底是什么——你希望发现什么？Stephen Sherry 博士：所以大脑问题是一种遗传性生成疾病，我父亲去年夏天做了检测，那让我开始思考这件事。但 NIH 和基因组研究所已经有一个 12 年的项目，主导了寻找 Eric 今天早上如此精彩地提到的这些变异目录。而且，你知道，我们在 NCBI 的任务之一就是维护那个目录，试图将其与疾病联系起来，所以，你知道，我一直在做这个。我就是那种[听不清]社交型的人，坐在计算机房里——[笑声]——试图发布准确的数据。我个人一直想知道这对我意味着什么？你知道，我对正在出现的疾病没有任何，你知道，个人了解。我认为我面临的遗传性疾病并不多。所以并不是那种

[38:54] 好奇心，更多的是我会如何——但一个是，你知道，我看到所有这些自愿把他们的基因型放入公共科学数据库的人，你知道，并且处理那些数据，我应该对企业有同样程度的承诺。所以这是一个个人决定，我会把这些数据公开，只是因为它对别人的要求不超过我对自己的期望。以及我在操作数据库和确保，你知道，所有同意都得到遵守方面所付出的谨慎。你知道，我想从参与者的角度理解这个过程。这就是我说的，我从未参加过研究，所以这是一种消费者驱动的方法。而且我认为正如 Sharon 所说，应该有更多这样的做法，人们非常感兴趣。

[39:37] 价格合适，你知道，在圣诞节，而且并不是我父母特别生病或什么的。我只是想他们什么都有，但你能给他们什么，会是对他们自身的了解。而我们发现的是，它在我们家里引发了很多关于科学、关于这些研究如何获得资助以及我们正在学到什么的对话。这变成了讨论时刻，我认为其范围远比健康问题更广泛，它关乎公共研究如何真正与美国人的生活相关。所以我发现作为一个钩子，他们不理解我做什么。他们从研究生院起就不理解，现在它相关了。所以我认为这对许多美国人来说可能是一个更广泛的机会。

[40:19] Sharon Terry：很好，观众席怎么样？我们想留一些时间让你们提问。有两个麦克风。男性发言者：那很棒。我在想问问小组成员，除了 Watson 博士，他们是否有兴趣进行重新测序，这样就能告诉我们过去使用的技术与新技术[按音拼写]相比，以及衰老的影响。你们想重新测序吗？James Watson 博士：我——可能吧，你知道，我这个年龄的人有 80% 听不见，所以——[笑声] 男性发言者：我同意你。

[40:58] Sharon Terry：所以问题是——Misha Angrist：你想重新测序吗？James Watson 博士：不。[笑声] 不，我是说，唯一的事情是对那个东西里的 tom[按音拼写]序列进行测序[听不清]，而且，你知道。但我——不，他们做得相当好，而且——[笑声] 任何，你知道，结果[听不清]他们说：“我们看了你的序列，你与坏的那个相差一个碱基对。”所以我从不，你知道，我从未处于风险之中。而且——但我尽量不做一个担忧者，所以我尽量避免会让我担忧的信息。所以这就是为什么我，你知道，而——我想强调，这些细胞色素在医学治疗中确实相当重要，那是我们可能应该——我只能说，除了小公司在做这件事，没有别的方式，那

[42:03] 平均——那会足够快地到达普通人。但你应该与心脏病专家打交道，你知道，这是一个[听不清]。但是，你知道，谁来支付这些信息等等，但在我的情况下它很重要。β受体阻滞剂确实能控制血压，[听不清]它们对血压有效。而且正如我了解到的，80% 的 80 岁以上的人确实——血压到了你必须控制它的程度。而且，你知道，我——男性发言者：[听不清]关于临床[听不清]参与者。这个基因组——为动脉钙化发现的基因与 Gall 博士[按音拼写]及其团队[听不清]疾病测序的外周动脉钙化基因有任何相似性吗？

[42:52] [笑声] 男性发言者：[听不清] 男性发言者：我想[听不清] 73，如果我没记错的话。James Watson 博士：你有一个问题[听不清]——[笑声] Sharon Terry：继续，Rick。你可以——是的。Rick Del Sontro：答案是我就是不知道。我道歉。Bert Gold：我是 Bert Gold。我在国家癌症研究所。

[43:25] 我必须说，沃森博士，我七岁时第一次见到您，而且我毫不怀疑，如果您想另谋职业，您完全可以去说单口喜剧。[笑声] 您绝对和杰瑞·宋飞一样出色。[掌声] 詹姆斯·沃森博士：不，那会给你惹麻烦。伯特·戈尔德：好的。詹姆斯·沃森博士：在学术——伯特·戈尔德：我的问题是问沃森博士的。我有幸查看了他在达菲基因座[按发音拼写]区域的DNA，所以我了解到您至少是达菲杂合子，这暗示着像我们其他人一样，您有某种非洲起源，但也许在某种程度上您的起源比我们其他人更近一些，然而我听到您有点否认或对此不确定，或者更多地认同苏格兰或爱尔兰血统，所以我想知道

[44:29] 您是怎么想的。您认为这是DNA错误还是您有什么想法？詹姆斯·沃森博士：我没什么想法。[笑声] 卡里·斯蒂芬森有理由不喜欢我；我也有理由不喜欢他。[笑声] 你知道，我曾经在一次会议上叫他水蛭。伯特·戈尔德：是亲切地叫。詹姆斯·沃森博士：不。[笑声] 不，你知道，他是冰岛人，身高大约六英尺八英寸，而且他，你知道，他像克雷格·文特尔[按发音拼写]。我是说，你知道，他们——那是个很强的个性。

[45:11] 而且他做过——像克雷格一样，他做过一些好事，我不是想说，你知道——不。但是，你知道，你不会不至少[听不清]就在《纽约时报》上发表文章，为什么他认为我，你知道，这确实让我去看了一些祖先，但——我是说，照片，你知道。但是——莎伦·特里：所以他有很好的理由说明他从哪里得到——詹姆斯·沃森博士：这有点无关紧要，我只是——我只是在讲笑话，因为我坦白说根本不在乎。

[45:45] [笑声] 莎伦·特里：下一个问题。男发言者：所以我想知道我能否请各位专家谈谈他们认为这类数据今后会存储在哪里，因为很可能会有多个供应商、多家公司、多种技术能够对你的DNA进行测序。你可能拥有自己序列的多个副本，你将如何跟踪这些？你能否——消费者会自己处理吗，还是必须有一个可信的中央存储库为他们跟踪？那里有很多未解决的问题，我只是好奇你们对此有什么评论。

[46:15] 斯蒂芬·谢里博士：我认为他们会像对待音乐下载一样对待它。我认为它会是个人文库，或者会有私营公司进入那个市场。除了为了个人的效率或便利之外，我不认为出于任何原因需要集中化。我不认为它适合放在政府数据库中，因为它不是研究，也不是为此资助的。我知道，你知道，我正在做的和别人已经做的将会进入公司数据库。它们可能会被出售，然后转到某个新公司，你知道，这一切都在知情同意书中。我打算保留一份个人副本。我会下载它并那样整合起来。这是你的经验吗？

[46:56] 米沙·安格里斯特：我认为它会——对大多数人来说，它可能存在于云端，而一些更担心隐私的人会坚持让它，你知道，放在他们的床头柜上或其他地方，而不是放在公共或远程位置。男发言者：谢谢。里克·德尔·桑特罗：我只是以为苹果正在为此开发一个应用，我没有——[笑声] 莎伦·特里：你可以看出他是个企业家。是的。女发言者：大家好，我是莱拉[按发音拼写]。

[47:27] 我是这里的一名遗传咨询学生。所以我想指出，我猜，你们所有人可能有一个共同点，那就是当你们决定做这件事时，你们有很多——首先，你们与那些为你们做这件事的人有某种程度的关系，你知道，在某种程度上。而且你们对自己做了什么、没看到什么、谁做的以及整个过程如何展开有很大的控制权。我猜我想知道你们是否认为那是早期采用者的特权，还是你们认为每个人都有权享有？如果是后者，那么一旦这变得更普遍，你们将如何扩大规模？抱歉，很啰嗦，但是——詹姆斯·沃森博士：我没听懂那个。

[48:08] 莎伦·特里：里克，你想先试试那个吗？里克·德尔·桑特罗：嗯，是的，我是说，对我来说有点像是，老实说；我不知道发生了什么。我是说，所以，你知道，看看——获取信息，我很乐意与任何人分享。我很想，你知道，每当我——我是说，我实际上还没看过任何数据，对吧？

[48:40] 我只是拿到结果。所以我实际上还没看过它是什么样子。所以我确信如果我要求，我可以看。但对我来说，只是我很乐意分享它，我很高兴它在那里。我个人不必为此付费，它是作为研究的一部分付费的。所以我非常幸运，据我了解，做全测序相当昂贵，你知道。所以，我是说，我想这是我能给出的最好答案。米沙·安格里斯特：我认为这是个很好的问题。我认为作为早期采用者我们享有特权，我们得到了很多手把手的指导。然后，当然，做的人越多，这就变得难以扩大规模。你如何为每个人提供有血有肉的遗传咨询？所以这，我认为，在某种程度上催生了世界上的23andMe。甚至个人基因组计划，也有一个动向

[49:43] 远离与社区医学遗传学家之间这类亲密互动，更多地转向软件，因为我不知道还能怎样扩大规模。Stephen Sherry 博士：再补充一点，因为这正是我在这个过程中的处境——试图决定把结果开放到什么程度。我的父母非常关心确保我能看到他们的数据，但目前这仅限于我们的直系家庭。我们想要一种清晰的方式，在其他人接受检测时与我们的大家庭分享这些数据。然后，一旦我们看到了结果，就向全世界开放。我不认为自己已经准备好，在完全不知道会有什么后果的情况下，就说它像个人基因组那样公开了。我相信你要事先做出承诺，对吧？这是知情同意的一部分。所以我认为，在消费者模式下，这会更循序渐进，而清晰地提供并架构这一点，我认为对于这项技术惠及晚期采用者时的伦理至关重要。

[50:43] 男发言人：所以，正如你刚才提到的，你会愿意将这些数据与世界分享。你会把你的遗传信息分享给保险公司吗？现在问这个问题可能有点早，但作为经历过这件事的人，你希望你的保险公司知道这件事吗？如果不希望，他们对此持什么立场？Misha Angrist：你会把你的数据分享给保险公司吗？James Watson 博士：当然会，但我认为，你知道，如果我是在管理这些大项目之一，我会，你知道，只对大约 70 岁的人进行测序。

[51:25] [笑声] 不，不——一个原因是你能获得他们完整的既往病史，而不是反过来。总的来说，退休的人不一定担心把信息公开。而且我认为，除非我们有一些与基因型相关的表型，否则将很难解读。所以如果我们过分强调保密，我想说的是，我之所以不担心，部分是因为我的年龄。

[52:02] 你知道，他们不会，我也不会，他们不会发现亨廷顿病的杂合基因，你知道。所以——我认为重要的是，很多人要意识到他们更有可能受益，就像我通过查看[听不清]而受益，这样我就能帮助我的儿子，仅此而已。而且你可能会发现自己携带囊性纤维化的基因，因此你的孩子应该检查这个。所以我认为——总的来说我不会担心测序，我认为这被夸大了。

[52:45] Sharon Terry：关于保险问题还有其他想法吗？Misha Angrist：嗯，我的意思是，除了他的——Jim 的 APOE 位点[按发音拼写]之外，我们的基因组都是公开的，所以保险公司不必问我们。James Watson 博士：是的，但他们没有 tom-T，他们真的没有解读所需的数据，所以你必须真正回去重新查看它，然后你就能做出非常可怕的预测，而不是，你知道，如果你有三个，就是 50%，现在如果是三个长的，就是 80%。所以，你知道，我认为这是一个你真正必须——我会建议人们不要去了解它，或者，你知道，不要让它被公开，因为没有任何好处。

[53:34] Stephen Sherry 博士：你认为保险公司如果拥有这些信息，会用它做些什么吗？James Watson 博士：嗯，我们——目前法律禁止他们使用它，我想。Francis[按发音拼写]推动通过的这项了不起的法律，我认为你不能受到歧视。Misha Angrist：在健康保险和[按发音拼写]就业方面？Sharon Terry：对。James Watson 博士：是的，坦率地说，我认为那是我们最不用担心的事。Stephen Sherry 博士：我只想补充一点，我认为分享我的遗传信息和表型信息之间是有区别的。而这正是我妈妈对其中一些——23andMe 调查——他们在表型上收集的内容——的一个担忧。

[54:13] 我只想说，她确实反对收集胸罩尺码。[笑声] Misha Angrist：我想说的另一点是，这可以是双向的，所以如果我知道我是 ApoE4[按发音拼写]的纯合子，而我没有与任何人分享这个信息，那就没有什么能阻止我大量购买长期护理保险。所以——Sharon Terry：对，所以我们将接受最后两个问题，我们会请小组回答得非常简短，以便我们能按时结束。我想我们在这边。

[54:48] Ahmed Kablan：Ahmed Kablan[按发音拼写]，NIDDK[按发音拼写]。你认为为每个人进行基因组测序是否是一件——是否是正确的事情，并告诉他们可能存在的 SNP[按发音拼写]或可能的遗传疾病发展情况，因为例如，告诉他们你患有这种疾病，一旦他们患上这种疾病，与告诉他们可能在 20 年后患上阿尔茨海默病或痴呆症是不同的，因为知道这只是一个预测，而不是确定的事实。因为，再次，除了遗传学之外还有其他因素[听不清]，[听不清]，环境因素和其他因素，也许有些人无法很好地接受这个消息，他们可能会崩溃。就像如果我知道我会脱发，我可能会在脱发前拍一百万张照片。所以，你认为这对每个人来说都是一件合适的事情吗，即使[听不清]每个人都能进行基因测序？

[55:43] Sharon Terry：Rick，你看起来好像—— Rick Del Sontro：是的，这是个很好的问题。我得出的答案是，不，并非如此。它并不适合所有人，我认为需要有一些筛选。我想 Watson 博士之前已经说过，究竟该告诉人们什么，对吧？因为我认为那可能是，你知道，看，有些人就是爱担忧的人。Watson 博士不是那种人；他避开担忧，这很好。这就是为什么他是，你知道，你现在多大，73 了吗？[笑声] Dr. James Watson：那倒不错 [按发音拼写]。

[56:14] Rick Del Sontro：但我想这就是关键所在，有些人能够较好地应对这些信息，有些人则无法很好地应对。当然，从某种角度来看，如果那是某种真正灾难性的情况，你会想知道吗？那会改变我认为你每天看待和回应生活的方式，而那可能并不健康。但如果有些事情是你可以控制的，对吧，是你知道的，那对你来说很重要，那些事情就是我想了解的那类事情。就像你说的，如果我注定会得亨廷顿病，我不确定我一定会想知道。

[56:49] Dr. James Watson：不，我会起诉那个告诉我的医生——[笑声]——因为，你知道，不必要地搞乱了我未来的生活。Rick Del Sontro：是的，因为并不能保证你一定会得。我是说—— Dr. James Watson：我认为你得有点常识。Misha Angrist：如果有人想知道呢？Dr. James Watson：如果他们想知道，当然可以，你知道。Male Speaker：算是个法律问题—— Dr. James Watson：[听不清] 但是，我是说，他们在冒很大的风险。但是，你知道，发现 [听不清] 你可以告诉我，如果我——我会得亨廷顿病，你得它的几率太低了，所以不算——但阿尔茨海默病是更现实的一个。

[57:25][] Male Speaker：算是个法律问题，学术媒体和普通媒体上都有相当多的讨论，关于基因组中各种序列的专利化。如果我们知道了 Watson 博士特定的基因组赋予了他幽默能力，能不能——你对能够为此申请专利并只保留给我怎么看？或者我会把它卖掉。[笑声] Male Speaker：我会发财的。Dr. James Watson：不，我因为在这里、因为反对 [按发音拼写] 那个而被解雇了，所以我对这件事有长期的看法，他们只是——他们让遗传学倒退了，这就是我想说的全部。他们—— Sharon Terry：好吧，那么，Misha，你对此有最后要说的吗？

[58:13][] Misha Angrist：嗯，正如这个听众中的大多数人可能知道的，纽约的 Sweet 法官去年裁定 Myriad Genetics 败诉，涉及他们对 BRCA 基因的一些专利，该裁决目前正在上诉中。我认为这些专利中的大多数无论如何都将在本十年内到期。我预计单基因疾病的基因专利可能会自然消亡，也许那是痴心妄想。

[58:47][] Sharon Terry：很好，我们听取了各种各样的人的意见，他们以各种方式、从各种不同的预言中了解了自己的序列。我认为 10 年前我们不可能举办这个专题讨论会，所以从某种意义上说，我们已经走了很远。今天早上当我听 Eric 给我们提出百万基因组的目标，或者给我们另一个 [按发音拼写] Eric，我认为我们还没有开始探索在社会背景下这样做意味着什么。如果我们在 10 年前说，我们能够把书卖给世界各地每一个阁楼和地下室里的彼此，我们会说那太疯狂了。而今天我们做起来相当容易。所以我认为我们也会发现，随着这些需求的出现，随着个人自己站出来成为 NIH、Wellcome Trust [按发音拼写] 以及世界各地其他实体的合作伙伴，我们将能够共同解决这些问题。

[59:36][] 而且我们真的能够建立希望，而不是炒作。所以我想请你们大家和我一起感谢这个专题讨论小组。[掌声]

查看英文原始字幕

[0:00] Mark Guyer: Welcome back to the afternoon session. Iím Mark Guyer. Iím the director of the Division of Extramural Research at NHGRI and Iím going to take over moderating this afternoon so that Eric can relax, which is an oxymoron if I ever heard one. Iím going to just continue with the approach that Eric began and invite our panel members up. And introduce Sharon Terry, President and CEO of the Genetic Alliance, who is going to moderate the panel discussion.

[0:34] Sharon Terry: Thanks very much, Mark and thanks to the planning committee for a really wonderful day so far. And I think the afternoon will be equally wonderful. The brilliance of the planning committee -- you all can take your seats -- is such that they were wise enough to know that the people and the various forms of association with their own genomes needed to be a part of this symposium as well. And I come to this because I have two children with a recessive disease called pseudoxanthoma elasticum. Iím a college chaplain by trade, but now very much in this world and very happy to be part of it. My -- I am also very much in association with all the information weíve watched this morning and waiting, just like much of the public, for the kinds of solutions, therapies, tests, et cetera that we hope to see. My brother died of glioblastoma multiforme, so I was

[1:34] happy to see that as an early entry into the various programs. And then Iím very good friends with Progeria Foundation and several of the others that weíve mentioned so far. Iím also a person who did 23andMe almost as soon as it was available and more recently enrolled in ClinSeq [spelled phonetically], which we are going to hear a little about today. So Iím very interested in our own genome and what we can do with the information. Iíd comment that I think collecting samples as we go, that was certainly mentioned several times this morning and said to be very difficult, will be just like many of the other things we thought are going to be very difficult. And that is it wonít be once we allow the right systems to be put in place including the involvement of citizen scientists, people who understand that they need to be involved, and by that, I really mean all of us, that every one of us, especially through social networks, will begin to understand the importance of being available for science in various ways.

[2:27] Today, weíre going to hear from a number of individuals who have had their genomes sequenced and who have a great deal of interest in understanding this on an individual basis. And weíre going to ask them to answer two questions in a very brief introduction that theyíre going to give us. And then weíre going to ask them to ask each other questions and then weíre going to invite you to ask them questions. So this particular panel which lasts about one hour is going to be a little more interactive than some of the other sessions. So you should be ready to ask these individuals anything you want.

[2:57] Iím also going to dispense with formal introductions and just give you their names and affiliations. And Iím also going to give you the order in which theyíre going to appear, although theyíre here already. So first, weíre going to hear from Dr. Stephen Sherry of the National Library of Medicine. Then weíre going to hear from Rick Del Sontro from -- whoís a ClinSeq participant. Weíre also going to hear then from Misha Angrist from Duke University, and then finally from Dr. James Watson from the Cold Spring Harbor Laboratory. Again, each of them will take about five minutes to introduce themselves and then weíll move into some conversation amongst them and then some questions from you.

[3:37] So, Steve [spelled phonetically], if you could begin. Dr. Stephen Sherry: Thank you, Sharon. So I guess I would like to say that Iím excited about the promise of biology in genomics. And Iíve done this professionally for about 10 years, 13 years at NCBI where I run, or Iíve helped develop variation resources, dbSNP and dbGaP being primary among them. And so Iíve had a scientific relationship with genomic information for my whole professional career and have watched with curiosity about how the consumer reagents are being developed and what this could mean to me personally. I have not participated in a medical research study before, but this year 23andMe put the genome typing kits on sale for Christmas, and so I bought them for my family. And thought this would be something neat to give my parents for a Christmas present, they had everything you know, so what do you give them?

[4:31] [laughter] Now itís going to be an obsessive set of questions about, you know, their drug sensitivity to statins and all sorts of things. I havenít received my results yet, so unlike others on this distinguished panel, I donít have a lot to say about how this has changed my thinking. I can maybe speak briefly to why I decided to do this [unintelligible] trivial curiosity. In developing these catalogues, these resources, at NCBI weíre very concerned about the relationship we have to participants in medical research studies. Their volunteer spirit, their trust is essential to the relationship in scientific research. And so weíre trying to ensure that the resources we develop at the Library of Medicine are responsive to their needs as well as to the needs of the research community.

[5:15] What we imagine is that going forward, genomics are going to be more available to consumers and -- but it wonít be every consumer that is coming forward to look for information. Mostly likely there is going to be a key person in each family who took biology in college or knows some genetics and will be the person that is the authority in a family relationship, the go-to person to say, ìInterpret my genetic test.î In my personal experience, my parents have come to me and said, you know, my father has a degenerative brain condition, what does this mean, you know, their tests. And so Iím looking at them now, not as a theoretical researcher making sure the information is complete, but trying to interpret the data personally for my own family members. And so Iím thinking that the more I can become engaged with 23andMe and these other information providers that are digesting information, that itíll help us inform our design decisions and the resources in the information structures that we provide at the Library because weíre trying to serve everybody, taxpayers included, with our research community. Itís kind of [unintelligible] -- Iíll stop there.

[6:16] Sharon Terry: Great, thanks very much. Rick? Rick Del Sontro: Well, I come at it from a completely different angle. Iím not a scientist, Iím just a layman. My storyís kind of interesting. I bought into the myth that if I was physically active, if I ate properly, if I kept my cholesterol in check, and had low triglycerides and, you know, I was on the road to success. And having had a mother who died at age 69 during her third open heart surgery, having had a grandfather who died of heart disease as well who was one of the first 100 people to get open heart surgery, I was always sensitive to that. And a few years back, my sister at the time was, I believe, was 48 years old and she started to feel not right. So she went in and she saw a doctor who sent her over to see a cardiologist. Long story short, she -- it turned out that

[7:20] she had three blockages, two of them they stented, one they did not, and she strongly encouraged the family to go get checked. Now, I come from a large family, thereís eight children. Interesting note, my sisterís cholesterol level, combined cholesterol level, was about 104 and remains there today without taking statins because she -- her body doesnít do well with them. So, anyway, on that I went to see my doctor who, you know, again, Iíd seen for years just the regular practitioner who put me on the treadmill with an EKG machine which basically was only going to tell me I guess if I was ready to keel over from a heart attack. So I checked out fine and went home. I had a brother at the time who was 38, cholesterol level roughly 150, low triglycerides, physically active, and he went in and got a nuclear stress test. They didnít like what they saw, did a catheterization. He went in

[8:21] for emergency double bypass surgery at the age of 38. So I panicked, went and saw a cardiologist. And he walked into the room and said, looked at my file and said, ìWhat are you doing here?î And I said, ìLook, just let me tell you my story and if you really want me to leave after that, Iíll just leave.î So I told him and he thought it was interesting. And told me to go and get a heart scan done, which I did. It came back that my calcification was through the roof. So at that point in time, I went through a number of tests. He said that the only way weíll really know whatís going on is if we do the catheterization, thatís the only way youíll get any piece of mind. So I did, and fortunately for me none of my blockages were severe enough that they needed to stent them. And as I was lying there in recovery, for -- I think you had to lie on your back for four or five hours, someone came over to me and said, ìTheyíre doing a study over at NIH called, you know, with ClinSeq. You might be interested in this

[9:23] and you might be a good person, a good candidate to go over there.î So I called and called and somebody finally called me back. And I said, ìYeah, Iíll participate.î [laughter] Well, they were busy doing research, you know, lot of DNA out there, you know. So anyway, I went in and told them my family history and they were real giddy about the whole thing to be honest with you as I was going through and telling them, you know, what had gone on and what was going on. And so, they did a bunch of tests that day and about a month or so later, I got a phone call and I could -- I really didnít understand, but I could tell that they were excited about something. And they said, you know, ìWe think weíve come across something pretty, pretty interesting here.î And I said, ìOkay, great.î And they said, ìDo you think your entire family would be willing to participate in the study?î I said, ìSure, but theyíre not all here local.î They were like, ìOh, donít worry about it, you know, just see if theyíll come in and theyíll participate.î So, you know, I got in touch with all of them and said, ìWould you guys be game, go in

[10:25] for study. Theyíre doing a study on, you know, heart disease and your DNA.î Yeah, okay, theyíll go. And so I think from there it sort of has blossomed is the best way I can put it. The study has gone layers and layers now, and in fact I was just talking to Dr. Biesecker [spelled phonetically] before I came in and theyíve done some, you know, family history and theyíve traced ancestry back to Italy. And I think heís going to be going over there to make a trip and theyíve now tested extended family, cousins, and things of that nature. And I personally have been fully sequenced, so I went through that, had no idea what it was. They said, ìWow, do you know what that is?î I said, ìNo, I have no clue as to what that means.î [laughter] [unintelligible] and Dr. Watson, I donít mean to, you know, I just -- [laughter] -- sorry about that. Iím a layman, Iím just a guy. So anyway, they said, you know, ìAs we go through the sequencing, we come across things that we find, do you want to know about

[11:32] them?î And I thought to myself, ìWell, yeah, I think I do.î So they said, ìGreat.î So I got a call one day right before Christmas and they said, you know, ìCan you come in?î and, ìWe found something and we want to talk to you about it.î And Iím like, ìOkay, well when do you want me to come in? Well, no, Iím leaving for the holidays and oh, well then the doctor is away for a week after that, and so itíll be, have to be like mid-January.î And Iím like, ìOh, well, can you give me an idea of what youíve found?î ìNo, weíre not allowed to do that.î [laughter] Oh, this will be a good Christmas, right? So anyway, it turned out that they found a condition called HNPP, which during the sequencing -- and if you donít know what HNPP is, itís okay because I didnít know either. But basically I get numbness; I get sporadic stages of numbness throughout my body. Itís been going on since I was about 20 years old. I had no idea what caused it and nobody else could tell me what caused it candidly. And parts of my body could

[12:34] go numb for days or weeks or even months. And then ultimately it would go away. And so I got to learn a lot more about that and subsequently also got to learn some of the things that I am potentially, I am a carrier for. Most of them seem to be, you know, obscure, so nothing really to worry about. But Iíve been asked before how has this changed me? How has this impacted me, what does it mean? Itís really been interesting because I did the study not necessarily for myself, maybe not even for my children, but for my childrenís children because I thought there would be a point in time when, you know, youíre born and there you have it, your blueprint is right in front of you and you know what to do. I liken it to using a GPS, right, so youíre going down the road and youíre going to run into traffic and your GPS is going to tell you to take a turn the other way. Thereís nothing you can do, youíre getting from point A to point B, but along the way you might -- there might be better ways to go, right? There might be better things for us to do to prevent things or avoid certain

[13:36] situations. And so from my standpoint, I want to know. I know thereís a lot of people out there that I talk to that probably say, ìLook, I donít want to know whatís going on.î But for me itís been important to know, itís been very eye-opening. I will say this, the energy and the excitement of everybody on the staff at the ClinSeq study has been amazing. Itís really -- theyíre just very excited about the work that they do and from my perspective, thatís pretty neat. So hopefully thatís a good background, probably took over five minutes, but thatís my story. So thanks.

[14:10] [applause] Sharon Terry: Thank you. Misha Angrist: Well, thatís a tough act to follow. So I got involved in this -- Iím not going to talk about clinical utility or even personal utility, but maybe existential utility. I spent from the age of 25 to 35 or so in a human genetics lab. I was the board eligible genetic counselor. And then I studied a birth defect and we actually found some Mendelian mutations. We were not a CLIA certified lab; we could not give results back to those patients and families. Eventually we became a CLIA certified lab, but that sort of disconnect from the people we were studying always sort

[15:12] of stuck in my craw [spelled phonetically]. And so many years later, I opened up Scientific American because there was a story in there called ìGenomes for All,î written by a guy named George Church at Harvard. And I read that article and I felt like here was a guy who was articulating many of the things that I had felt, that the time had come to sort of start thinking about how do we put this technology out into the world, at what point do we start sequencing healthy people like the gentleman to my right? And so that sort of started this odyssey of my enrolling in George Churchís personal genome project and getting my genome sequenced and living with it and making it public and thinking about the implications of it. And spending a lot

[16:17] of hours in front of Excel spreadsheets and learning a lot about next generation sequencing technology. And so, here I am. [applause] Dr. James Watson: It was now I think almost five years ago when the founder of 454, a new company [unintelligible] DNA sequencing came to my office, he telephoned me and said he wanted to -- they had this instrument that would be able to sequence me at a reasonable cost and would I be the first person to be sequenced? So I said yes, right away. I didnít -- I said, might as well make it public, but I donít want to

[17:19] know anything about apolipoprotein E because I have a grandmother who died of Alzheimerís in the late í90s -- no, mid í90s. And it was pretty awful, so I didnít want to know anything about it. And then really didnít think about and two years passed and he called me up and said, ìYouíre half sequenced and weíre working with Houston Genome Center, Gibbs and the group -- and George Winsock [spelled phonetically] was the key.î And then with time, you know, I went down to Houston and there was publicity for the Genome Center for the Baylor College of Medicine and they told me I was heterozygote for a lot of bad genes. They said I had a variant of the breast cancer, BRCA1. Okay, but, you

[18:26] know, I didnít know what that meant and I donít think they did either. But they told me I was homozygous for something like a terrible disease DNA repair [spelled phonetically] like Helmanís Disease [spelled phonetically]. I mean, you just donít reach my age if you had that, so I just didnít think about it. And -- but I did think that if, you know, I didnít know which variant I had in the breast cancer gene, so I thought I should tell my nieces because it is an awful gene if youíve got the Jewish variant. Weíre not Jewish, so, you know I didnít think I should have it.

[19:02] [laughter] But I wanted to find out and -- but before calling them, I called Mary-Claire King [spelled phonetically] and my sequences on the Web. So she looked up and called me back and said you have a harmless Irish variant. How she knows that itís a harmless Irish variant, but, you know. So I didnít think about it again, didnít call my nieces, and so didnít think much about it. And then someone called me up and said, ìYou havenít deleted or let me know that you havenít deleted enough from your sequence [unintelligible] apolipoprotein is, do you want to know?î Of course, I didnít want to know and I couldnít tell them donít publish it and, you know -- but the story is more complicated.

[19:57] Then something actually useful happened, an article appeared from Craig Venterís [spelled phonetically] that compared his sequence with mine with regard to the cytochrome P-450, the enzymes which metabolize drugs. And Craig was fine, but I had a very slow metabolizing form of 2P6 [spelled phonetically] something, the one which not only metabolizes beta blockers, but antipsychotics. So itís an important one. And I had been put on beta blockers and they had put me to sleep and I had to go off them. And then suddenly I had the explanation, that instead of taking one every day, I should maybe take one a week, which Iím now doing and it controls my blood pressure. So that was extremely useful fact which I wouldnít have known without -- it was also the question came up where someone said, ìWell, in getting

[21:02] yourself sequenced, you are going to know something about your children. Do you have the right to invade their privacy?î Okay, no, no, I mean, thatís the sort of thing that these, you know, these bioethicists have nothing better to do but to think about. [laughter] And -- it turned out my son, I have a son who is schizophrenic, and he had been given antipsychotics after he had hit the doctor, who was a Freudian, and I would have hit any Freudian too.

[21:35] [laughter] But anyways, he hit the doctor, a really miserable, fat, little man, and Chestnut Lodge [spelled phonetically], itís gone now, but it was a place outside of [unintelligible] and he went into neuroleptic malignant syndrome and almost died. I think we now have the explanation, he didnít metabolize the drugs. And so itís a very useful fact. He doesnít want his DNA sequenced, but I know was homozygous, so heís heterozygous. And it turns out probably the -- that some psychiatrists are really measuring this now before they give out antipsychotics to schizophrenic people, so itís quite important. And if I was younger and, you know, living on an academic salary, I would certainly start a company to do just the cytochromes because no one who, you know, who goes to a doctorís office for blood pressure should be given

[22:37] the drug without knowing whether you can metabolize it. I mean, some people are -- Iím a slow metabolizer, some are super fast, it never works. So it probably would be cost-effective for the big health insurers to do it. So I think, you know, and then the only other thing is after a, you know, remark I never intended to make, Kari Stefansson [spelled phonetically] announced in The London Times that I was -- he had looked at my genome and I was 16 percent black and four percent -- six percent Asian, and it didnít go with the pedigrees of my family. And he never published how he concluded that I was 16 percent black and six percent Asian, probably, you know, the Asian probably means that one of the Watsons [spelled phonetically] in Tennessee consorted

[23:38] with an Indian woman. [laughter] And -- but I just have no interest in it. So, you know, I could have followed it up. I havenít sent my DNA to 23andMe which could give me really quite a good ancestry. But Iím afraid, I, you know, live with the myth that Iím only English, Scotch, and Irish, no Welsh, and -- [laughter] -- so I donít want it disturbed [spelled phonetically]. You know, itís a myth and why destroy my myth? It might discover I have German blood or something, you know, that I wouldnít have wanted. So, you know, thatís where I am, I am remarkably uncurious. And -- but what I have been surprised is that, you know, people really havenít looked at my sequence and written about me that they found out something. So there seems to be a total lack of interest in me as far as I can tell.

[24:39] [laughter] You know, people giving me good or bad. Then it turns on the Alzheimerís; whoís interesting, me [spelled phonetically]. One thing that 454 canít do is count Ts [spelled phonetically], you know. And it turns out that apolipoprotein E, the key to it, the work of Allen Roses [spelled phonetically] is that adjacent to it is a gene called tom-D [spelled phonetically] standing for the Aldrich [spelled phonetically] mitochondrial membrane, itís a pore [spelled phonetically]. And people have either a long one -- or depending, itís very closely linked to the aprol [spelled phonetically], so the three has its own poly -- tom-T [spelled phonetically] polymorphisms. And thereís a long sequence of about 50, which is very bad prognostic for Alzheimerís. If you had that long sequence and youíre three, youíre going to -- no, probably 80 percent chance youíll get Alzheimerís. If you have the short one, youíre pretty safe. And so, those who would have never been measured and you would have to go back to

[25:48] Sanger [spelled phonetically] sequencing to do it, or Pacific BioSciences could do it. Craig, having released his entire sequence, you know, it would be interesting looking him up to look at his tom-T and if I were Craig, I wouldnít look at it because heís 60, you know, getting old.

[26:19] [laughter] And, you know, people do, you know, a bad four [spelled phonetically] with a long tom-T means you have a chance of Alzheimerís in your 60s. Sharon Terry: Thanks, Jim, so you [inaudible] -- [laughter] Dr. James Watson: Anyways, so thatís the [inaudible] the story, so -- but I think that just to come back to the general point. I think DNA sequences should be known. I donít think the average person should really ever look at them. And I donít even think the average doctor can look at them, thereís going to have to be consultants.

[26:52] The doctor says, whatís the message from the genome that I should -- I can better treat my patient. And then the doctor has to show sense of not telling you that we found out that youíre going to die of Huntingtonís, you see. Because, you know, thatís not good news. So thereís got to be old fashioned medicine and common sense by which you only tell people things which are useful and donít tell things which are just another reason for worry. I donít see any way to regulate it, it just depends on -- I wouldnít want it regulated.

[27:37] Itís complicated enough, I donít know how you can even get a certificate that you know youíre competent to look at a genome and predict someoneís future. Sharon Terry: Great, thanks Jim. Dr. James Watson: Okay, well thatís -- [applause] Sharon Terry: So I think you teed [spelled phonetically] up a really good question and one thatís a very interesting one thatís been debated since genomes were available to those of us who are lay public and even those of us who are scientists but working in the various fields. And that is the -- who should know what, when, and who should be telling who what? And I think of even -- there is a new tool out by 5AM Solutions [spelled phonetically] called Snip Tips [spelled phonetically]. And essentially you download the 23andMe sequence and it flags every snip you read about in any article, and you can click on it and it shows you your variance.

[28:20] So more and more, thereís tools that make it very much available to each of us to look at these things. And I wondered if some of you would comment on, what do you think you should know, who do you think should be telling you what you know or donít know? And also thatís the kind of common perception, at least among the scientific community, that none of this is ready for what they say is prime time. Dr. Stephen Sherry: I just talked to my parents last night about this thinking about today and asking them what they hope to know when they get their results back in a few weeks. And theyíre very interested in the pharmacodynamic set of cytochrome results and their sensitivity to drugs. Theyíre in their 70s and theyíre starting to look at statins and other issues, and want to know when findings come out about drug sensitivities or dosing. Is it relevant to them? And I think itís a great, you know, kind of personal use. And so theyíre, I think, looking for either their doctor to interpret their results or a professional, you know, that they [spelled phonetically] would be referred to, a qualified professional. I donít think that occupation is really flushed out

[29:22] yet. Dr. James Watson: It doesnít exist now [spelled phonetically]. Dr. Stephen Sherry: So the Web is going to do that for them, itís going to be these Web services, 23andMe themselves, itís a monthly subscription model where as new findings are published, you can go reinterpret [spelled phonetically] your genome or like what you mentioned. And so I think there is a question about how do -- how accurate are they or do they oversimplify? Thatís the risk that Iím wondering about. Dr. James Watson: I would be very afraid to trust the Web, you know, for something thatís fairly important. I called Mary-Claire King, I was lucky because she knew all the variants in BRCA1 or you know, [unintelligible] would let her know about. That the -- I think weíre going to have to have some experts, that you just donít believe that, you know, this database is perfect. I mean, the decisions are too important and I would, you know, in the sense of a second opinion now, I was lucky and knew the, you

[30:26] know, the person who probably knew BRCA1 as well as anyone in the world and how you get this advice. But I do think thereís going to eventually have to be human beings that you trust that they know all the polymorphisms, and theyíre doctors, and they donít want to practice. But they sort of specialize in, you know, all the genes of your immune system or, you know, they really know about arthritis. You get help from them. So I think thereís got to be sort of specialties of people that you can call. Just because itís on the Web and, you know, whoís put it there and how, you know, has the FDA certified it, and if they have, you know, I wouldnít, you know, the data is so old you wouldnít want to use it.

[31:21] So, you know, again, you know, the whole thing will favor people who are rich and who can get good advice and with time, it will percolate down. I donít see much that will change the situation. Dr. Stephen Sherry: Can I ask if you see a difference between a physician that orders a test, returns it, doesnít know how to interpret it, and hands it to the patient and the company that just does it for profit and just returns it to the patient? Dr. James Watson: I think I feel [spelled phonetically] responsible because, you know, if you give it to Eric, he can, you know, interpret it, but most people wonít know what it means. Itís just too complicated.

[32:01] Dr. Stephen Sherry: Thatís been my parentsí experience in the diagnostic tests in this brain disorder. It was ordered, the genetic tests came back, the physician said, ìI donít know how to interpret this,î and handed it to my father. Dr. James Watson: Yeah, so I think, you know, with time there will be virtually -- whether they call it a medical specialty or something. A lot of people who donít like to deal with human beings, you know, are autistic people, they can be in charge of the significance of the data and they never have to talk to the poor person whoís sick. No, I mean, Iím really looking at this for the first time in human history when these informatics people who are unsocial have -- [laughter] -- we have a real need and they have jobs.

[32:52] Dr. Stephen Sherry: If we open the data -- Dr. James Watson: What? Yeah. Misha Angrist: So youíre saying this is a public works program. Dr. James Watson: No, no, no, no, no, I think youíve got to eventually -- someone has got to pay for someone to look into genome. I asked George Church, I said, ìWhat does my genome mean?î And he said, ìWell, youíll have to give me money, it costs money to examine someoneís genome.î So -- you know, and not an inconsiderable sum, probably to get your genome, and I can easily see $10,000 or $20,000 expended [spelled phonetically] to have someone look at it. And in the sense the cost will go up, both go up and down, because thereís going to be so many more regions we can look because we have some experience that that polymorphisms mean something. And we can have this all on an NIH Web, but I think for something, you know, before we were scared shitless of learning

[33:59] something, you should get a second opinion. Thatís all Iím trying to say. Sharon Terry: Letís hear your thoughts on that. Misha Angrist: Well, so in quote, unquote preparation for this, I went on SNPedia [spelled phonetically] last night because all of my data are there. This was a website that was essentially started by two guys in their basement that links out to the literature, all of the GWAS and Genetic Association literature, and so I have, I donít know, 9,000 or 10,000 annotated genotypes there. And it makes some subjective evaluation, these seem to be the most interesting snips and itís based on allele [spelled phonetically] frequency, and severity of condition, et cetera. And so I looked at the top of the list, I said, ìI wonder what my most interesting snip is,î and it says, ìYou are male.î

[35:05] [laughter] Sharon Terry: Which we now know is important after this morning. Misha Angrist: I thought they nailed that. [laughter] And then, you know, it was followed by some other sort of phenotypically [spelled phonetically] obvious, if not flattering things like, you know, 7X [spelled phonetically] risk of male pattern baldness and that sort of stuff. And so we can say thatís frivolous and we donít need to know that and whatís the point. But I guess I see that as sort of an educational tool that, yes, I know I am going bald, but hereís an opportunity to maybe understand why, and to look at any of these biochemical pathways that have been discussed so eloquently here today and to just get an insight into perhaps at some superficial level how this

[36:12] affects me. Sharon Terry: Great. Dr. James Watson: Good luck. [laughter] Misha Angrist: Iíve got time. Rick Del Sontro: Yeah, I sort of -- I think Iím kind of in Mishaís camp here on this one. Again, I mean, there -- when I did the testing, it was really about my children and their children. So if there was something that I found, there was something that they could find that potentially could impact them or would impact them, is there something that, you know, could be done to prevent it or keep them from going down a, you know, a slippery slope with things. So -- but itís been interesting. Itís been interesting to at least try to understand things and why theyíre happening to me and even just, you know, just the one condition. But I think in listening to Dr. Watson, it becomes evident that there are much more critical issues that you could find that I think would

[37:17] be of concern. And I would be, you know, itís sort of like my general practitioner just putting me on a treadmill with an EKG machine saying, ìHere, you have no heart disease.î You know, I donít fault the guy, but by the same token, I probably could have found out years ago that, you know, maybe I could have done something to prevent it. So my other thing, if I could ask a question of, I wanted to ask Dr. Sherry and -- two things. One, you got the tests for, you said, for Christmas? You know, Valentineís Day is Monday, what have you got in preparation for that?

[37:51] [laughter] No, I mean -- what was it, was it your parents that inspired this? Did you want to learn more about what could cause this, you know, the brain issue? And what was it that really -- and what are you hoping to find? Dr. Stephen Sherry: So the brain issue is a heredity generative condition, my father got tested for last summer and that was -- got me thinking about it. But there has been a 12-year enterprise NIH and the Genome Institute has lead about finding these catalogues of variants that Eric mentioned this morning so nicely. And, you know, one of our tasks at NCBI has been maintaining that catalogue, trying to relate it to disease and so, you know, Iíve worked it. I am one of those [unintelligible] social types that sit in a computer room -- [laughter] -- and try to put out accurate data. Iíve always wondered personally what would it mean to me? You know, I donít have any, you know, personal knowledge of disorders that are coming up. Thereís not a lot of hereditary disease that I think I am facing. So it wasnít that

[38:54] curiosity, it was more of how would I -- but one is, you know, I see all these people that volunteer to put their genotypes into public scientific repositories, you know, and working with that data, I should have that same level of commitment to the enterprise. So it was a personal decision, I would put this data out just because itís asking no more of anyone else than I would expect of myself. And the care that I take in operating the database and making sure that, you know, all of the consent is followed. You know, I want to understand that process from the participantís side. Thatís what Iím saying, I have never been in a study, so this is a consumer-driven approach to that. And I think as Sharon was saying, there should be more of that, people are very interested.

[39:37] The price was right, you know, at Christmas and it wasnít like my parents were particularly sick or anything. I was just like they have everything but whatís something that you could give them would be knowledge of themselves. And in weíre finding is that itís starting a lot of conversations in our family about science, about how these studies are funded and what weíre learning. And thatís turned into discussion moments that I think that are much broader than just the health question, itís about how public research is really relevant to American lives. So Iím finding that as a hook, they donít understand what I do. They havenít understood since graduate school, now itís relevant. So I think that could be a broader opportunity for a lot of Americans.

[40:19] Sharon Terry: Great, how about from the audience? We want to leave some time for you to ask some questions. Thereís two microphones. Male Speaker: That was great. I was thinking of asking the panelists, except Dr. Watson, if they are in interested in getting resequenced so that will tell us about the technology that has been used in the past versus new [spelled phonetically] versus the effect of aging. Do you like to get resequenced? Dr. James Watson: I am -- probably, you know, 80 percent of people my age canít hear, so -- [laughter] Male Speaker: I agree with you.

[40:58] Sharon Terry: So the question is -- Misha Angrist: Would you like to get resequenced? Dr. James Watson: No. [laughter] No, I mean, the only thing would be to sequence the tom [spelled phonetically] sequences in the thing [unintelligible] and, you know. But I -- no, they did a pretty good job and -- [laughter] Anything which, you know, it turned out the [unintelligible] they said, ìWe looked at your sequence, youíre one base pair off from the bad one.î So I never, you know, I was never at risk. And -- but I try and not be a worrier and so I try and avoid the information which will worry me. So thatís why I, you know, whereas -- and I want to make the emphasis, these cytochromes are really quite important in medical treatment and thatís information which probably we should -- and I canít say any way except small companies doing it, that

[42:03] the average -- that will reach the average person fast enough. But you should deal with cardiologists, you know, itís a [unintelligible]. But, you know, who would pay for the information and so on, but in my case it was important. Beta blockers really do control blood pressure, [unintelligible] they work for blood pressure. And as I learned, 80 percent of people above 80 have really -- blood pressure to the point where you have to control it. And, you know, I -- Male Speaker: [unintelligible] on clinical [unintelligible] participant. Did this genome -- gene that has been found for arterial calcification has got any similarity with the peripheral artery calcification gene that has been [unintelligible] sequenced by Dr. Gall [spelled phonetically] and his group [unintelligible] disease?

[42:52] [laughter] Male Speaker: [inaudible] Male Speaker: I think [unintelligible] 73, if I could recall. Dr. James Watson: You had one question [unintelligible] -- [laughter] Sharon Terry: Go ahead, Rick. You can -- yeah. Rick Del Sontro: The answer is I just donít know. I apologize. Bert Gold: Iím Bert Gold. Iím at National Cancer Institute.

[43:25] I must say, Dr. Watson, that I saw you the first time when I was seven years old and thereís no question in my mind that if you want another career, that you could always do standup comedy. [laughter] You are absolutely as good as Jerry Seinfeld. [applause] Dr. James Watson: No, it gets you into trouble. Bert Gold: Okay. Dr. James Watson: In an academic -- Bert Gold: My question is for Dr. Watson. Iíve had the great honor to look at his DNA in the region of the Duffy locus [spelled phonetically] and so Iím aware that you are at least a Duffy heterozygote, which would suggest that like the rest of us, you have some origin from Africa but perhaps yours is a bit more recent than some of the rest of us at some level, yet I hear you kind of disavowing or not being certain of that or identifying with Scottish or Irish ancestry more, so Iím wondering

[44:29] what you think. Do you think it was a DNA mistake or what are your thoughts? Dr. James Watson: I have no thoughts. [laughter] Kari Stefansson has reason to dislike me; I have reasons to dislike him. [laughter] I called him a leech once at a meeting, you know. Bert Gold: Affectionately. Dr. James Watson: No. [laughter] No, you know, heís Icelandic, about six foot eight in height and heís, you know, heís Craig Venter-like [spelled phonetically]. I mean, you know, they -- itís a strong personality.

[45:11] And heís done -- like Craig, heís done some good things, Iím not trying to say, you know -- no. But, you know, you donít publish in The New York Times without at least [unintelligible] why he thinks Iím, you know, it did cause me to look at a few ancestors but -- pictures, I mean, you know. But -- Sharon Terry: So very good reasons for where he gets -- Dr. James Watson: Itís sort of irrelevant, Iím just -- Iím telling jokes because I donít frankly give a damn.

[45:45] [laughter] Sharon Terry: Next question. Male Speaker: So I wonder if I could ask the panel for their thoughts on where they think this kind of data is going to be stored going forward given the fact that there is probably going to be multiple vendors, multiple companies, multiple technologies being able to sequence your DNA. You could have multiple copies of your own sequence, how are you going to be able to keep track of this? Are you going to be able to -- are consumers going to handle it themselves, or is there going to have to be some central repository thatís trusted that can keep track of it for them? Thereís a lot of open issues there, I am just curious what your comments are on that.

[46:15] Dr. Stephen Sherry: I think theyíll treat it like music downloads. I think itíll be personal libraries or there will be private companies that step into that market. I donít think it needs to be centralized for any reasons other than efficiency or convenience for individuals. I donít think itís appropriate in a government database because itís not research, itís not funded for that. I know that, you know, what Iím having done and what others have done are going to be in a company databases. They may get sold and then that goes to some new company and, you know, thatís all in the informed consent. I plan on keeping a personal copy of it. Iíll download it and consolidate it that way. Is that your experience?

[46:56] Misha Angrist: I think itíll -- for most people, itíll probably live in the clouds and some people who are more worried about privacy will insist that it live, you know, on their nightstand or whatever and not in a public or remote location. Male Speaker: Thanks. Rick Del Sontro: I just thought Apple was building an app for that, I didnít -- [laughter] Sharon Terry: You can tell heís an entrepreneur. Yes. Female Speaker: Hi there, Iím Layla [spelled phonetically].

[47:27] Iím a genetic counseling student here. And so I wanted to just point out, I guess, something that you all maybe have in common, which is that when you decided to do this you had a lot of -- you had relationships, first of all, with the people who were doing it to you for some, you know, to some extent. And you had a lot of control over what you did and didnít see and who did it and sort of how the process unfolded. And I guess I wanted to know whether you think thatís an early adopterís prerogative or do you think everybody has the right to that? And if so, if the latter, like how would you scale that up once this is more common? Sorry, very wordy but -- Dr. James Watson: I didnít understand that.

[48:08] Sharon Terry: Rick, do you want to try that one first? Rick Del Sontro: Well, yeah, I mean, for me it was sort of, Iíll be honest; I didnít know what was going on. I mean, and so, you know, to look at the -- and get access to the information, Iím just happy to share it with whomever. I would love to, you know, whenever I -- I mean, I havenít actually seen any of the data, right?

[48:40] I just get the results. So I havenít actually looked at what it looks like yet. So I am sure if I asked, I could. But for me, itís just Iím happy to share it, Iím happy itís out there. I personally didnít have to pay for it, it was paid for as part of the study. So Iím very fortunate in that, it is my understanding that itís fairly expensive to do, you know, full sequencing. So, I mean, I think thatís the best answer I can give. Misha Angrist: I think itís an excellent question. I think we are privileged as early adopters, that we got a lot of handholding. And then, of course, the more people do it, that becomes a difficult thing to scale. How do you provide flesh and blood genetic counseling for everyone? And so this, I think, to some extent, gives rise to the 23andMeís of the world. And even the Personal Genome Project, there is a move

[49:43] away from sort of these intimate interactions with the neighborhood medical geneticist and more toward software because I donít know how else you can scale up. Dr. Stephen Sherry: Just add one point because this is where Iím at in the process in trying to decide how open to make the results. And my parents are very concerned about ensuring that I can see their data, but right now itís just our immediate family. We want a clear way to, you know, to share these with our extended family as other people get tested. And then once weíve seen the results, open it to the world. I donít think Iím ready to, you know, having no idea whatís coming to say itís out there like personal genomes. I believe you make the commitment up front, right? Itís part of the consent. So I think that on the consumer model, it will be more incremental and to have that clearly provided and architected, I think, is essential for the ethics of this as it reaches the late adopters.

[50:43] Male Speaker: So, as you just mentioned, you would be open to the possibility of sharing these data with the world. Would you share your genetic information with insurance companies? This maybe a little bit early on in the process to ask this, but as somebody whoís gone through this, you know, would you want your insurance company to know about this, if not, where do they stand on this? Misha Angrist: Would you share your data with insurance companies? Dr. James Watson: Sure, but I think, you know, if I were, you know, running one of these big projects, I would, you know, sequence only people who are about 70 years old.

[51:25] [laughter] No, no -- a reason is that you have their entire past medical history rather than going, you know, the other way. And on the whole, people who are retired, they are not worried about necessarily putting the information public. And I think unless we have some phenotypes correlated with genotypes, itís going to be hard to interpret it. So if we emphasize too much secrecy, so Iím trying to get at, I didnít worry in part because of my age.

[52:02] You know, they werenít going to, I wasnít going to, they werenít going to find a hetero-gene for Huntingtonís disease, you know. So -- I think itís important that a lot of people realize that they are more likely to benefit, like I benefited by looking [unintelligible] so I could help my son, thatís all. And that you could discover youíre a carrier for cystic fibrosis and therefore your children should look at this. So I think -- I wouldnít worry about sequencing for the most part, I think itís overblown.

[52:45] Sharon Terry: Other thoughts on the insurance issue? Misha Angrist: Well, I mean, with the exception of his -- Jimís APOE locus [spelled phonetically] our genomes are both public, so insurance companies donít have to ask us. Dr. James Watson: Yeah, but they donít have the tom-T, they really donít have the data that they need to interpret, so you have to really go back and now look at it and then you can make really pretty scary predictions instead of, you know, if you have the three, itís 50 percent, now if itís three long, 80 percent. So, you know, I think itís one you really have to -- I would advise people not to learn it or, you know, not to have it released because thereís no benefit.

[53:34] Dr. Stephen Sherry: Do you think that the insurance companies would do anything with the information if they had it? Dr. James Watson: Well, weíre -- right now theyíre prohibited by law of using it, I think. This wonderful law that Francis [spelled phonetically] got through, I think you canít be discriminated against. Misha Angrist: In health insurance and [spelled phonetically] employment? Sharon Terry: Right. Dr. James Watson: Yeah, I think thatís the least of our worries frankly. Dr. Stephen Sherry: I would just add that I think thereís a difference between sharing my genetic information and the phenotypic information. And that was my momís one concern on some of these -- the 23andMe surveys, what they collect phenotypically.

[54:13] And Iíll just say that she really objected to bra size. [laughter] Misha Angrist: I think the other point to make is that this can cut both ways, so if I know that I am homozygous for ApoE4 [spelled phonetically] and I have not shared that information with anyone, there is nothing to stop me from loading up on long term care insurance. So -- Sharon Terry: Right, so weíre going to take the last two questions and weíre going to ask the panel to be very brief so that we can get back on time. And I think weíre over here.

[54:48] Ahmed Kablan: Ahmed Kablan [spelled phonetically], NIDDK [spelled phonetically]. Do you think sequencing the genome for everyone is something -- is the right decision to do and telling them that they might have in terms of SNPs [spelled phonetically] or possible genetic disease development because, for example, telling them that you have this disease, once they have this disease is different from telling them that they might be developing Alzheimerís or dementia in 20 years from now knowing that it is only a prediction, not a certainty. Because, again, other factors [unintelligible] besides genetics, [unintelligible], environmental factors and others and maybe some people, they will not be able to take the news well and they might lose it. Like if I knew I am going to lose my hair, I might take a million pictures before I lost it. So, do you think thatís a suitable thing to do for everyone even if it [unintelligible] that everyone can do the genetics sequencing?

[55:43] Sharon Terry: Rick, you look like you -- Rick Del Sontro: Yeah, thatís a great question. The answer that I come down on is, no, itís not. Itís not for everyone and I think there needs to be some filtering. I think Dr. Watson said it earlier of exactly what you do tell people, right? Because I think that could be, you know, look, there are people that are worriers. Dr. Watson is not one; he avoids the worry, thatís good. Thatís why he is, you know, what are you, 73 now? [laughter] Dr. James Watson: That would be nice [spelled phonetically].

[56:14] Rick Del Sontro: But I guess thatís the point, there are people who would deal okay with the information, there are people that would not deal well with it. And certainly from the standpoint if it was something really catastrophic, would you want to know? That changes the way that, I think, you look and react to life every day and that probably wouldnít be healthy. But if there was something that you could control, right, that you knew, that would be important to you, those things are the kinds of things that I would like to know about. Like you said, if I was going to have Huntingtonís disease, I donít know that I would want to know that necessarily.

[56:49] Dr. James Watson: No, I would sue the doctor who would tell me that -- [laughter] -- for, you know unnecessarily messing up my future life. Rick Del Sontro: Yeah, because thereís no guarantee youíll get it. I mean -- Dr. James Watson: I think you have got to have some common sense. Misha Angrist: What if someone wants to know? Dr. James Watson: If they want to know, sure, you know. Male Speaker: Sort of a legal question -- Dr. James Watson: [inaudible] but, I mean, theyíre taking a big risk. But, you know, finding [unintelligible] you can tell me if I -- Iím going to get Huntingtonís disease, the chance of your getting it is so low that itís not -- but the Alzheimerís is a more real one.

[57:25] Male Speaker: Sort of a legal question, there is considerable discussion in the academic and regular press about patenting of various sequences in the genome. If we knew Dr. Watsonís specific genome that gave him the humor capability, could -- what do you feel about being able to patent that and reserve it for just me? Or Iíll sell it. [laughter] Male Speaker: Iíd be rich. Dr. James Watson: No, I got fired for being here, for opposing [spelled phonetically] that, so Iíve had a long view of this thing that theyíre just -- they set back genetics, thatís all Iím trying to say. Theyíre -- Sharon Terry: All right, well, Misha, did you have a last word on that?

[58:13] Misha Angrist: Well, as probably most in this audience know, Judge Sweet in New York last year ruled against Myriad Genetics, some of their patents on BRCA genes and that decision is now being appealed. I think most of these patents are set to expire this decade anyway. I expect gene patenting for monogenic diseases will probably die of natural causes, maybe thatís wishful thinking.

[58:47] Sharon Terry: Great, well, weíve heard from a variety of individuals who have learned about their sequence in a variety of ways, from a variety of different prophecies. I think 10 years ago we wouldnít have been able to have this panel, so in a sense weíve come a very far way. And this morning when I listened to Eric give us a charge for a million genomes or give us another [spelled phonetically] Eric, I think we have not yet begun to explore what it means to do that in a social context. If we had said 10 years ago would we be able to sell books in every attic and basement across the world to each other, we would have said thatís crazy. And we do it today quite easily. So I think we are also going to find that as these needs arise and as individuals themselves step forward to be partners with NIH, with Wellcome Trust [spelled phonetically], with other entities around the world, that we are going to be able to solve these problems together.

[59:36] And weíre really going to be able to build hope and not hype. So I want to ask you to all join me in thanking the panel. [applause]

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《探索你的基因蓝图——由 Sharon Terry 主持的专题讨论》由 National Human Genome Research Institute（https://www.youtube.com/@genometv）制作，依据 CC BY 3.0（https://creativecommons.org/licenses/by/3.0/）许可。源视频：https://www.youtube.com/watch?v=_xGRLcHiHLo。本页是该视频的文本转录，添加了段落分隔和时间戳；创作者与 Vidleaf 无关联，也不为其背书。Vidleaf 添加了 AI 标点和 AI 生成的摘要；原始措辞仍可在本页查看。

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最后更新于2026-10-20

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